Test 2 Notes and Review
Test 2 Notes and Review 85033 - GEN 3000 - 002
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Extensions and Modifications of Basic Principles if 2012 Pearson Education Inc Vocabulary Allele different forms of a gene as in D or d Same gene among individuals but different allelescombinations Lossoffunction mutation The allele isn t doing what it s supposed to be doing sometimesnot always Null aee Complete loss of function Gainoffunction mutation Supposed to make pink But it makes red It s overachieving Neutral mutation May not change the phenotype but at genetic level you can see the different in alleles As in you have red Still making red And making red doesn t change But you can see some sort of different in the alleles at genetic level Gene interaction We can also have two genes that interact with each other to create a product Something depends on two genotypes XIinkage On sex chromosomes How does it change what we seeexpect to see in the next generation Identification Capital vs lowercase Usually capital is dominant Lowercase is recessive Wildtype vs mutant vs Wildtype normal Anything that deviates mutant H or just without and no Superscripts can be placed on labelling the alleles Incomplete Dominance G generation Purple fruit White fruit r X 3 PP pp Cametes t J i K F 1 generation Violet fruit Violet fruit CametesQ L L J Fertilization l KFZ generation Violet Violet PP White Conclusion Genotypic ratio Phenotypic ratio 1 purple2violetl white lPP2Ppl pp Ratio of COMPLETE dominance would be 31 l i Table 32 Phenotypic ratios for simple genetic crosses crosses for a sangle locus Ratio Genotypes of Parents 3l Aa gtlt Aa l2l Aa gtlt Ac 1 An x an A0 x AA Uniform progency AA x AA an x cm AA x an AA X Aa Note A line in a genotype such as A Genotypes of Progeny Type of Dominance 34 A 3 l4 a 4 AA 392 Aa 4 aa 2 An 2 aa 2 An 2 AA All AA All an All An All A indicates that any allele is possible Dominance Incomplete dominance Dominance or incomplete dominance Incomplete dominance Dominance or incomplete dominance Dominance or incomplete dominance Dominance or incomplete dominance Dominance Codominance IVIN blood types antigens on red blood cells Two alleles LM and NI Possible Genotypes ND ND L3939L39I Phenotypes L39V39L39Vl Only produce M antigen LNLN Only produce N antigen L39V39LN Produce BOTH M and N antigen Table 51 Differences between dominance incomplete dominance and codominance Type of Dominance Definition Dominance Phenotype of the heterozygote is the same as the phenotype of one of the homozygotes Incomplete dominance Phenotype of the heterozygote is intermediate falls within the range between the phenotypes of the two homozygotes Codominance Phenotype of the heterozygote includes the phenotypes of both homozygotes Table 51 GeneticsA Conceptual Approach Fourth Edition 2012 W H Freeman and Company Codominance example Codominance example Positions to which hemo QIOPins haVe Hemoglobin types Phenotype Genotype m39grated Origin present 1 1 l Sicklecell s A Hb Hb S and A trait o I Sickleeell Hbs Hbs D S anemia Normal HbA HbA D A Migration Phenotype of blood is Codominant both A and S are seen Phenotype of person may be considered recessive Yellow Mice Lucien Cu not 1905 Showed that lVIendel s principles applied to animals Gray x White gt 3 gray 1 white Most of the time Yellow x Yellow gt low 1 gray Assumed nyYy 139 3 yellow 1 gray KP generation Yellow Yellow J X Yy I Gametes L l J J Fertilization F1 generation Dead Yellow Nonyellgw a kl4 V4 YY quot R 12 Yy Dominant effect on color Lethality is recessive Pleiotropy one gene Conclusion YY mice die and so 23 of progeny are Yy yellow 13 of progeny are yy nonyellow that impacts several aspects of the overall phenotype Dominant lethal one copy causes death Ex Huntington 5 Disease MLM hets do not have a tail deformed spinal development so dominant allele for spine development MLML fail to complete embryonic development so recessive for death Multiple Alleles Can be many different alleles for one gene in the general population ABO blood group A codes for A antigen B codes for B antigen 39 codes for no antigen IAgti IBgti AB Multiple Alleles ABO blood group Blood Types AB individual has IA and IB allele 0 has neither IA and IB allele so ii b Bloodrecipient reactions to a V lyPhg thypg a Genotype Antigen Antibodies blood type type made by E 1 body 6 donorblood antibodies 39 l gt162 i m 39o 1 i l v v v t 3 mtgremand TFT39L 5 5 waesll r 239 A g Mates y 39 rquot 7vb amp1 mtgpetites IAIA A or A B 1A1 IBIB B or B A 13239 AB IAIB AandB None 0 ii None AandB TABLE 41 Multiple Alleles Some of the Alleles Present at the white Locus of Drosophila Allele W W67 2012 Pearson Education Inc Name White whiteapricot Whitebuff whiteblood Whitecoffee whiteeosin white mottled orange whitesatsuma white spotted whitetinged Eye Color pure white yellowish orange light buff yellowish ruby deep ruby yellowish pink light mottled orange deep ruby ne grain yellow mottling light pink AalAlB x AalquotB Consideration of pigmentation alone Consideration of blood types alone III mama 34 pigmented m gt 1 4 albino 3 I gt 1 4 type B Genotypes Phenotypes Genotypes Phenotypes Consideration of both characteristics together Of all offspring Of all offspring Final probabilities 14 A gt 316 pigmented type A 34 pigmented 24 AB gt 616 pigmented type AB 14 B gt 316 pigmented type B 14 A gt 116 albino type A 14 albino 24 AB gt 216 albino type AB 14 B gt 116 albino type B Final phenotypic ratio 316 616 316 116 216 116 2012 Pearson Education Inc Gene Interactions Example 1 Genes at two loci interact to produce single characteristic P generation Red Green 39 gtlt RR CC rr cc L Y J Cross K Fl generatlon Red k Rr Cc R dominant Red color r recessive no color C dominant decomposition of chlorophyll green pigment c recessive allele allows chloro to remain F1 generation Rr Cc X L Y Cross k KF2 generation Red Brown Yellow Green 916R C 316 R cc 316 rr C 116 rr cc Conclusion 9 red 3 brown 3 yellow 1 green P R dominant Red color r recessive no color C dominant decomposition of chlorophyll green pigment c recessive allele allows chloro to remain Glowtn Factor Receptor Activation DNA Replicative Damage Senesoenoe Differentiation Hormones Ultra Violet Stress Response Fade Withdrawal Q 7 Ubiqurtination 4 D E2FIDP Target Genes Cycltn EA EZF123 cch cMyc p107 RanGAP TK DHFR PCNA H2A etc 39 Fast DEE mm Anoptosls Recessive epistasis BL b m IE E I izaillelh AFEI Iam Black Chocolate Yellow BBEE bbEE BBee BbEE bbEe Bbee BBEe bbee BbEe BBEE 8 l BbEe i bbee BE Be bE be BbEe BE BBEE BBEe BbEE BbEe BBEe BBee BbEe Bbee BbEE BbEe bbEE bbEe BbEe Bbee bbEe bbee Bombay Phenotype lt2 1952 Identified rare mutation in a woman in Bombay FUT1 fuoosyl transferase H antigen Necessary for A and B antigens to be added to BBC hh individuals type as 0 but can NOT receive 0 blood Reoessive Epistasis Dominant Epistasis ww plants I 1 Comp und AI Enzyme gt Compound B Y plants 1 Enzyme H The dominant allele The recessive W inhibits A to B homozygous yy conversion inhibits B to C conversion Wyy white 316 wa Yellow 116 wwyy green Table 52 Modified dihybrid 39phenolypic ratios due to gene interaction Genotype Type of Ratio AB Abb aaB aabb Interaction Example 933i 9 3 3 1 None Seed shape and endosperm color in peas 9324 9 3 4 Recessive epistasis Coat color in Labrador retrievers 123 12 3 1 Dominant epistasis Color in squash 97 9 7 Duplicate recessive Albinism in snails epistasis 962 9 6 i Duplicate interaction 15 15 i Duplicate dominant epistasis 1 33 13 3 Dominant and recessive epistasis 39Each ratio is produced by a dihybrid cross AaBb gtlt AaBb Shaded bars represent combinations of genotypes that give the same phenotype Remember Inheritance of genes follows Mendel s principles of segregation and indep assortment These are cases of how the genotypes interact Harlequin Autosomal Dominant Recessive Lethal Bigenic IVI locus H locus Harlequin 4quot v ul Vl U Nonharlequin Harlequin hM hm Hm hM hm I I I I 1 5 IE 5 5 I lethal harlequin black whit merle luin Table 53 Common genotypes in different breeds of dogs Breed Usual Homozygous Genes Other Genes Present Within the Breed Basset hound BB EE ay 0 S 5quot 5i Beagle a a BB s39F sp E e English bulldog BB A aV at E39 E ebr S s39 squot s Chihuahua A5 a as at B b E39 E e39 e S s squot s quot Collie BB EE a at s s Dalmatian ASAs EE swsw B b Doberman a at EE 55 B b German shepherd BB 55 aV a as at E39 E e Golden retriever A A BB 55 E e Greyhound BB A aV E e e S squot 5quot 5i Irish setter BB ee 55 A at Labrador retriever A As 55 B b E e Poodle 55 A5 at B b E e Rottweiler a at BB EE 55 St Bernard a a BB E39 E s39 squot s quot Most dogs in the breed are homozygous for these genes a few individual dogs may possess other alleles at these loci Source Data from M B Willis Genetics of the Dog London Witherby 1989 Table 53 GeneticsA Conceptual Approach Fourth Edition 2012 W H Freeman and Company Complementation Determining if Mutations are in the same or Different loci Example Harebell plants blue wt Mutagenize get three true breeding white plants A B and C plants Ax blue F1 all blue F2 34 blue 14 white B x blue F1 blue F2 34 blue 14 white C x blue F1 blue F2 34 blue 14 white So recessive allele of a single gene leads to mutant are the mutations all in the same gene or in three different genes COMPLEMENTATION TO THE RESCUE Cross homozygous recessive mutants and see if progeny have the wt phenotype Complementation Determining if Mutations are in the same or Different loci COMPLEMENTATION TO THE RESCUE Cross homozygous recessive mutants and see if progeny have the wt phenotype If different genes wt B Get a wt allele for E A J each gene so will have wt phenotype Complementation Determining if Mutations are in the same or Different loci COMPLEMENTATION TO THE RESCUE Cross homozygous recessive mutants and see if progeny have the wt phenotype If the mutation is in the same gene AWtXB lLt No matter what still A J homozygous mutant for allele Wild type IN1 INZ gene gene Mutant quotquot Mutant quot quot Mutant quot quot quot quot llll quot quot W1 w2 w1 w2 w1 w2 gene gene gene gene gene gene P White X White White X White Mutant quot5quot Mutant quot quot Mutant quot quot 1 quotsquot quot quot quotsquot quot quot w1 w2 w1 w2 w1 w2 gene gene gene gene gene gene P White S X White White X White 1 l No complementation Complementatlon 5 4 quot39 1quot gtEnzyme No substrate Enzyme 2 Enzyme 2 1 L I l Colorless No Colorless Colorless l precursor 1 kprecursor 2 l l precursor 1 H precursor 2 Block no enzyme 1 Mutation in the same gene Mutation in different genes Incomplete penetrance Genotype does not always produce the expected phenotype Penetrance Percentage of individuals having a particular genotype that express the expected phenotype If 45 out of 50 people exhibit trait Penetrance 4550 09 90 Expressivity Degree to which a character is expressed How extreme is it the range to which the mutation shows Other influences genes or environmental factors can alter the effect of a gene Phenotypic expression each oval represents an individual 00000 Variable penetrance O 0 T O 0 Q 0 Variable expressivity Variable penetrance and expressivity What can cause variable penetrance or expressivity Temperature effect Nutritional effect Imprinting Genes and the Environment a Reared at 200C or less Reared at temperatures above 300C Himalayan produces dark fur at extremities only when reared at 25 C or less temperaturesensitive allele Or if it s inbetween those temperatures it can be grey Norm of reaction range of phenotypes produced by a genotype in different environments Pigment produced in fur under the ice pack Unit 2 Test Sex Chromosomes Remember there are several different mechanisms of sex determination P generation Male Female Y m 1quot Cametes l J k F1 generation Sperm xx C x Q XY Female Male Eggs X XY C Female Male Conclusion 1 sex ratio is produced Drosophila chromosomes X Y mmquot gullquot XX Xlinked White Eyes in Drosophila Thomas Hunt Morgan first explained sexlinked inheritance found some traits were associated with one sex or the other Discovered that a single male in his fruit fly colony had white eyes 1910 suspected gene for eye color was on X sex chromosome L xi Xlinked White Eyes in Drosophila Assume W red is dominant over w white WW female x ww male Ww offspring Ww female x Ww male Expected WW wW Ww ww or 31 ratio of red eyes to white Xlinked White Eyes in Drosophila This cross suggests that white eyes were a simple recessive trait cross a homozygous dominant with homozygous recessive get heterozygous offspring expressing dominant trait a Redeyed female crossed with white eyed male P generation Redeyed female w x X X Whiteeyed male h XWY mm 1 Gametes G L J J t F1 generation Redeyed female Redeyed male WMZP Fertilization However an F2 females had red eyes while only12 of males had white eyes fzgenera on lt9 X X1L XY Red Red eyed eyed a femam mam 3 x xW XWY Red Vthe eyed eyed mmam mwe Condu on 392 redeyed females V4 redeyed males 4 whiteeyed males Xlinked White Eyes in Drosophila b Reciprocal cross white eyed female crossed with redeyed male P generation Whiteeyed Redeyed female male X XWXW XY m h Is the White eye trait on X chromosome 1 Cametes J J L F2 generation a WC 1 W W Red Red Fl generation g eyriile 5 Redeyed Whiteeyed 3 Xw xw XWY female male g hemlzygos y Have one copy of a gene In a a b diploid cell gtlt White White eyed eyed X XW WY female male Males can not be homozygous or heterozygous hm h cocjusiojzf I 4re e e ema es I4 whitgeyed females Gametes l t 332fes L l J J Fertilization Xlinked color blindness in Humans o Redgreen color blindness is due to lack of of green and red absorbing pigments in the cone cells of the eye The locus for these pigments are close together on the X chromosome a Normal female and colorblind male P generation Normal color vision Colorblind female male XX XCY hmh ee b Reciprocal cross Fertilization K i F generation G XXC XY Normal Normal Eggs color color vision vision female male Conclusion Both females have normal color vision males and P generation Normal Color blind colorvision female male XCXC XY hmh Gametes x gt35 1 XXC XCY Normal Color 5995 color blind vision male female Fertilization K i F1 generation SpermG Conclusion Females have normal color vision males are color blind F Xlinked Recessive Traits I Unaffected j female carrier O l 2 3 III T 1234 56 IV I I Affected male 2 3 l 4 5 4 78 bi39 678 Affected males do not pass to sons can pass to daughter as carrier Why Father passes Y to sons Unaffected daughter can then pass to sons appears more frequently in males get only one X chromosome so if mutatedthen disease occurs Example of Xlinked Recessive Hemophilia A Due to abnormal or missing Factor VIII involved in clotting Located on X chromosome I m Princess Edward Duke Victoria of of Kent SaxeCoburg Cquot D Queen Albert K Victoria K39quot 5 D O d D i d d b i O gt D Victoria Edward Alice LOUIS Alfred Helena Louise Arthur Leopold Beatrice Henry K VII of Hesse cw O a m EI El Wilhelm Sophie George V Irene Henry Frederick Alexandra Nicholas II Alice of Alfonso Eugenie Leopold Maurice of King of Czar Athlone XI King K Greece England of Russia 0f Spain j V i i amber IE it aim George VI WaIdemar Prince Henry Olga Marie Alexis Rupert Alfonso Gonzalo Juan Maria King of Sigmund Tatania Anastasia K England of Prussia Prussian RUSSian VI f E Royal Family Royal Family E 5 D E i Margaret Elizabeth II Prince Juan Carlos Sophia of Queen of Philip King of Spain Greece K England VII lj Princess Prince Prince Prince Elena Cristina Filipe Anne Charles Andrew Edward British Spanish Royal Family Royal Family Xlinked Dominant Traits II lt 6 a 91011 J l 575 l 2 5 8 Y Do not skip generations Affected males pass to all daughters none of sons Heterozygote females pass the trait to half of their sons and half daughters Ex Hypophosphatemia Familial vitamin Dresistant rickets bone deformations like rickets but vit D does not cure defective transport of phosphate so excreted instead of going into bone Males are usually more severely affected YIinked traits appear only in males O 2 3 IV r2 2 86 genes on the Y with only 20 protein products 36 traits have been linked to the Y Pedigree characteristics of autosomal recessive autosomal dominant X linked recesswe X linked dominant and Ylinked traits Autosomal recessive trait l Appears in both sexes with equal frequency Trait tends to skip generations Affected offspring are usually born to unaffected parents When both parents are heterozygous approximately 4 of the offspring will be affected Appears more frequently among the children of consanguine marriages Autosomal dominant trait i Appears in both sexes with equal frequency Both sexes transmit the trait to their offspring Does not skip generations Affected offspring must have an affected parent unless they possess a new mutation 5 When one parent is affected heterozygous and the other parent is unaffected approximately 392 of the offspring will be affected Unaffected parents do not transmit the trait XIinked recessive trait l More males than females are affected Affected sons are usually born to unaffected mothers thus the trait skips generations A carrier heterozygous mother produces approximately 2 affected sons ls never passed from father to son All daughters of affected fathers are carriers Xlinked dominant trait 1 Both males and females are affected often more females than males are affected 2 Does not skip generations Affected sons must have an affected mother affected daughters must have either an affected mother or an affected father 3 Affected fathers will pass the trait on to all their daughters 4 Affected mothers if heterozygous will pass the trait on to 2 of their sons and 392 of their daughters Ylinked trait 1 Only males are affected 2 Is passed from father to all sons 3 Does not skip generations SexInfluenced Characteristics KP generation Beardless Bearded S l I r m X 0 5 mm BbBb Cametes J F 39 generation I Bearded 6 Beardless 9 i 1 B LBb Sexinfluenced characteristics are determined by autosomal genes but expressed differently in males and females Bb bearded dominant in males recessive in females Males both homozygous and hets express beards Females only homozygous F1 generation Bearded 3 Beardless 9 Q 3 f BBb m m Fertilization k F2 generation Beardless Bearded Bearded Beardless Beardless Bearded d d d S S S 14BB l BBb 14BbBb 14BB 12 BBb 14BbBb P l 374 V4 Conclusion 34 of the males are bearded 14 of the females are bearded Os o39 39 V 39l J 2 39 a if v a 4 1 z6quoton quot I 6 ass9 John Adams John Q Adams Charles F Adams Pattern Baldness is a Our job as scientists is to ensure that urban legend are debunked John Adams John Q Adams Charles F Adams Pattern Baldness is a SexInfluenced Traitiiii Pattern baldness is autosomal can be inherited from either parent Men require only a single bald allele females require two Also allele is expressed weakly in females leading to usually mild phenotype in females Castration which probably not a good baldness control method limits baldness so male sex hormones likely influence expression of baldness allele SexLimited Characteristics l cm Sexlimited characteristics are determined by autosomal genes but expressed ONLY in one sex ZERO penetrance in other sex Cock feathering autosomal recessive HH males are hen feathered bottom pic Females are hen feathered Hh males and females are both hen feathered hh males are cock feathered females hen feathered Genomic Imprinting Mendel reciprocal crosses give identical results male x female or female x male Not true Xlinked genes cytoplasmic genes males and females do not contribute the same DNAs Genomic lmprinting occurs with autosomal genes males and females contribute equal number of genes but expression is affected by parental origin Genomic Imprinting Remember 1 We carry two copies of each gene 2 Sometimes only one copy is expressed but not always Genes are somehow marked during gamete formation or early in the embryo First evidence Haploid miceall male genome develop normal placentals abnormal embryo structures All female abnormal placentas normal embryo structures so both must contribute Genomic Imprinting PraderWilli syndrome Angelman syndrome PWS small handsfeet short stature mental retardation frequently become obese due to increased appetite Always INHERITED from father PWS is caused by the absence of segment 1113 on the long arm of the paternally derived chromosome 15 In 7080 of PWS cases the region is missing due to a deletion BUT in others no deletion detected both copies of 15 from mom uniparental disomy Genomic Imprinting Angelman syndrome Uncontrollable puppetlike movements laughter AS 50 have deletion in 15 like PWS If not deleted both copies come from father SO for normal development need one copy from each parent Genomic Imprinting IMPRINTING DOES NOT AFFECT ALL GENES Methylation of DNA epigenetic modifications may be at work Epigenetics genome modifications that cause functional differences but do not change the nucleotide sequence Cytoplasmic Inheritance g Q a gt Remember Mendel principles of segregation and qu l Independent assortment genes are on chromosomes in nucleibut e a 9 W Genes in the cytoplasm lRepllication of mitochonldrial a i b Mitochondria 37 genes 15 000 bp 6Qd circular genome 210 copiesmito gg Zygote inherits nuclear genes from both parents but all most cytoplasmic genes come from WA W f E g 49 Q 33gt 022 Q 3 Q69 mother I I R Iic tion fmitoch ndri 139 ep a 0 t 0 all Egg IS huge sperm IS small and all mIto are I gt Q a lt29 65639 In tall regIon not part of fusion 6 3quot a 69 gQU 5 ng mar I i O COO Affected females pass it to ALL children both male and female Males do not pass trait to children Cytoplasmic Inheritance Pollen plant 8 60llen Pollen Pollenlt 7 3 Seed plant 9 Whit Fouro clock plants variegated leaves 39 Variegation caused by mutation in gene Green Variegated needed to make green pigment encoded in chloroplast 39t3939 39 if e quote t quot k 73quotquot White White White White Flowers random segregation of chloroplasts t from variegated branch yields eggs with all normal chloroplasts green all mutated white and a mix of chloroplasts variegated Green Green Green Green I quot t e 3917 4 4 t It 39 39I 1 39 39 39 quot fl I V V x i 39 r 1 39 t White H White White variegated Green Green Green Variegated Variegated Variegated Genetic Maternal Effect P generation Dextral C Sinistral 9 QJ X 6 S S 55 l m l Cametes F1 generation Sinistral l 6 C i Jk PHENOTYPE is determined by GENOTYPE of mother In this case genes are inherited from both parents vs cytoplasmic inheritance but offspring s phenotype is determined by genotype of mother Snail shell coiling most have a right coiling shell dextral coiling S dominant Some have a left coiling sinistral ss offspring genotype does not impact this KF generation Sinistral 6 55 J L t 1 G J Selffert39l39zat39on k F2 generation Genotype is for dextral 3 N Sex influences on heredity Genetic Phenomenon Phenotype determined by Sexlinked characteristic Genes located on the sex chromosome Sexinfluenced Genes on autosomal characteristic chromosomes that are more readily expressed in one sex Sexlimited characteristic Autosomal genes whose expression is limited to onesex Genetic maternal effect Nuclear genotype of the maternal parent Cytoplasmic inheritance Cytoplasmic genes which are usually inherited entirely from only one parent Genomic imprinting Genes whose expression is affected by the sex of the transmitting parent Table 55 GeneticsA Conceptual Approach Fourth Edition 2012 W H Freeman and Company Sex Chromosomes Remember there are several different mechanisms of sex determination Sex Determination Sexual Reproduction Formation of offspring that are genetically distinct from parent Sex noun defined by phenotype of individual not genotype Monoecious one house has both female and male reproductive structures Dioecious two house individual has either female or male reproductive structures Sex Determination Mechanisms 1 Chromosomal Sexdetermining system 2 Genetic Sexdetermining system 3 Environmental Sexdetermining system Chromosomal sexdetermining system Remember Chromosome theory of inheritance genes are located on chromosomes and chromosomes are substrate for gene segregation History Henking 1891 Male insects had a strange body in nuclei X body McClung X body chromosome Female grasshopper cells had 1 more chromosome than males Stevens and Wilson 1905 Female grasshopper have two X chromosomes Also X in male cells with smaller chromosome called Y X and Y separate into different sperm cells while egg cells all get a single X KP generation Male Female Xf Xf Gametes L J Remember sex is associated with the K inheritance of a particular chromosome r Sex chromosomes Genes are therefore F1 generation on chromosomes Sperm 60 XX Eggs xx xv 9 XY Female Male Female Male Conclusiom 1 sex ratio is produced Chromosomal Sex Determination systems some plants insects reptiles all mammals XXXY XXXO simple system females have two XX males have single X 0 no chromosome At meiosis half sperm receive X other half get no sex chromosome Heterogametic sexthe sex that produces two different gametes homogametic sex the sex that produces identical gametes Birds 9 ZZZW male is homogametic female is heterogametic Female produces two different gametes half with Z chromosome the other half with W found in birds moths some amphibians and some fishes Haplodiploidy and the Social Insects KP generation Female 2quot Cametes Egg Egg l K Sperm J k j G generation v v n zygote 2n zygote Male Female Conclusion In haplodiploidy sex is determined by the number of chromosome sets n or 2n Some members of Hymenoptera have no sex chromosomes Males develop from unfertilized eggs Males are haploid single set of chromosomes Females are diploid 2 Genetic Sexdetermining system No obvious difference in chromosomes ie no sex chromosome Genes determine the sex of an individual Similar to chromosomal sexdetermining after all genes drive the sex determination Found in some protozoans and plants 3 Environmental Sexdetermining system Ex Common Slipper Limpet sequential hermaphroditism I 3 r r u x H I 39 7 I f v 7 39 h I I I pj k x quot I 39 r I V A 39 p a F 2 u 7 x l39 L t J U Exgt Alligator Warm temperatures during embryonic development produces males cool temps produce females Drosophila chromosomes X Y mmquot mlquot XX The Mighty Fruit Fly Drosophila melanogaster Nondisjunction Morgan scored 1237 flies in his first cross F1 all but 3 had red eyes 3 males had white eyes Morgan attributed this to random mutation Bridges a student of Morgan s found this occurred too frequently to be mutation hypothesized that X chromosome fails to separate in Anaphase l of meiosis nondisjunction d Metaphase I IL Anaphase I d Telophase I ll i Metaphase plate V I j So some eggs get 2 copies of XX while others get none a Whiteeyed female and redeyed male P generation Whiteeyed Redeyed female male 5 X W XWXW XY Normal meiosis came wee 656 L l J J F1 generation swm XXW XWY Eggs Redeyed Whiteeyed female male Conclusion Normal separation of chromosomes results in 2 red eyed females and 12 whiteeyed males Fertil39zation k j b Whiteeyed female and redeyed male with nondisjunction P generation Whiteeyed Redeyed female male 5 X XWXW XY Nondisjunction Normal in meiosis meiosis Cametes L J J x 39 KP generation Redeyed Whiteeyed metafemale female dies X Y quotquotquot Redeyed Dies male Conclusion Nondisjunction results in whiteeyed females and redeyed males Table 41 Chromosome complements and sexual phenotypes in Drosopma SexChromosome Haploid Sets Complement of Autosomes XA Ratio Sexual Phenotype XX AA 10 Female XY AA 05 Male XO AA 05 Male XXY AA 1 0 Female XXX AA 1 5 Metafemale XXXY AA 1 S Metafemale XX AAA 067 lntersex XO AAA 033 Metamale XXXX AAA 1 3 Metafemale Sex Determination in Drosophilia Females XX Males XY but Y does not determine maleness Instead ratio of autosomes to X determine sex genic balance system X has genes for femaleproducing effects autosomes have genes for male producing effects Sex determined by XA of X chromosomes of haploid sets of autosomes I Sex chromosomes X X X Y Table 41 y Chromosome complements and sexual phenotypes 1 in Drosophila SexChromosome Haploid Sets Complement of Autosomes XX AA XY AA XO AA XXY AA XXX AA XXXY AA XX AAA XO AAA XXXX AAA XA Ratio 10 05 05 10 15 15 067 033 13 Sexual Phenotype Female Male Male Female Metafemale Metafemale Intersex Metamale Metafemale Turner Syndrome gt f i H 26 Gfrtlr 3 lg 35 3 5 lg 13 17 M l at it 19 20 21 22 X Y Females do not undergo puberty immature female secondary sex characters Low hairline and folds of skin on neck are characteristic May have cognitive impairment sterility XQ Note no known cases of no X at all suggests an embryonic requirement 12000 female births 45 chromosomes X Klinefelter Syndrome a 2 345 55 35 a at z s 3 a 12 13 14 15 16 17 18 3 33 6 3 1 2 9 20 m 2 XXY 2005 DARRYL LEJA Males small testes breast enlargement reduced facialpubic hair One or more Y chromosomes Multiple X chromosomes can be XXXY XXXXY or XXYY Often sterile May have mild cognitive impairment 1500 male births Often undiagnosed 47 chromosomes sex chromosomes XXY PolyX Females TriploX syndrome XXX tall thin sometimes normal fertility normal intelligence 11000 female births XXXX XXXXX Normal female anatomy but have cognitive impairment severity increases with increase in of X chromosomes The role of sex chromosomes via studies of sexchromosome anomolies 1 X contains genetic info essential for both sexes at least one X is required 2 Maledetermining gene is located on Y see Klinefelter syndrome 3 The absence of Y yields female no matter how many X s you have always female because no Y 4 Genes required for fertility are on X and Y females need at least two Xs to be fertile 5 Additional X chromosomes are detrimental What about the Y chromosome is important for producing male phenotypes A few XX males have been identified how does this happen Development All humans have neutral undifferentiated gonads early in development If testes develop they secrete testosterone triggers male character development and Mullerianinhibiting substance degrades of female reproductive tracts In the absence of male determining gene neutral gonads become ovaries SRY Sexdetermining region Y was discovered in 1990 39 39 Short arm v V igtrmmmg found in all XX males centmmere SRY gene absent in all XY females Long arm lt Will cause XX mice to be males if engineered into genome V 39 Y chromosome Androgeninsensitivity syndrome Credit Ksaviano Other genes besides SRY can influence sexual development Persons with androgeninsensitivity syndrome have female sexual characters but no uterus oviducts or ovaries Testes are found in abdominal cavity These women are XY Androgeninsensitivity syndrome How SHYtriggers teste development testes secrete testosterone if no receptor for testosterone or defective receptor then no male characters Defect is on X chromosome Summary Genes for male and female secondary characters on autosomes control of expression is key SRY is one gene there are plenty of others that can lead to genotypic male but phenotypic female Table 23 Chromosomal Determination of Sex in Drosophila and Humans Sex Chromosomes Species XX XY XXY XO Drosophila 9 lt3 9 3 Human S lt3 lt3 9 Note 0 indicates absence of a Chromosome Dosage Compensation or how to deal with multiple Xs Because females have two copies of every Xlinked gene they should produce twice the amount of gene product as males Overcome by dosage compensation Fruit flies double the activity of genes on X in males Worms C elegans halves activity of genes on both X Placental mammals inactivate one X chromosome Barr 1949 observed darkly staining body in nuclei of cat cells Barr body Lyon 1961 proposed that Barr body was inactive X chromosome Lyon hypothesis X inactivation females heterozygous at X loci will express one allele or the other in a given cell Females are MOSAIC for expression of Xlinked genes Dosage Compensation or how to deal with multiple Xs Table 42 Number of Barr bodies in human cells with different complements of sex chromosomes Sex Number of Chromosomes Syndrome Barr Bodies XX None 1 XY None 0 X0 Turner 0 XXY Klinefelter 1 XXYY Klinefelter 1 XXXY Klinefelter 2 XXXXY Klinefelter 3 XXX TriploX 2 XXXX PolyX female 3 XXXXX PolyX female 4 Dosage Compensation or how to deal with multiple Xs Two alleles for orange coat X black fur and X0 orange fur Males XY or X Y so either black or orange but not both Females X X black XO X orange or XX tortoiseshell Dosage Compensation or how to deal with multiple Xs X inactivation Takes place early in development Inactive X remains inactive as do all somatic descendent cells X inactivespecific transcript XISD gene located on the X chromosome is requhed Only the copy of XISTon inactivated X is expressed l and it is expressed during inactivation Does not encode a protein but RNA it produces may bind to inactivated chromosome prevent transcription Chromosome Variation and Mules The Nature of Chromosomes Nuclear genome of a smallish deer 2N 6 Karyotype display of a complete set of chromosomes Chromosomal Mutations 1 Chromosomal rearrangements 2 Aneuploids the number of chromosomes is altered additiondeletion 3 Polyploids one or more complete sets of chromosomes are added Overview i r a v2 u N quotLNOJS11 if g e o 35 v E jquotrs 37 A v i 3quot 1 3 39 quot w quot quot gt V r39 39 4 a I w lt r r quot 12 N r v j I Lrnq ene IC mo and z r W v w my r a w I w t v fl 739 quotng v 4 rp 3 3x r J 39 quot39 e x 4 fi r bfi i v f F quot 739quot quotquot quotquotquot 39i TV l 5Hi KL v 1 i i J J 1 5 3 3 3 R9 kf39e39i W 391 SEQ From another chromosome Extra chromosomes Inversion W W W Gain of Duplication genetic material Chromosomal Rearrangements a Duplication A B C D E F G I IIIID Original chromosome H J Rearrangement A B C D E F E F C I llIIIIII Rearranged chromosome b Deletion A B C D E F G CIulIIID Hl Rearrangement K X A B C D C IIulID c Inversion A B C D E F C CI IIIID Y Rearrangement F A B C I 3 Cl C II IIIID d Translocation A B C D E F c IlInlIIII YJ M N O P R S 1 l Rearrangement A B C D Q CIIIll I I M N O 2l39 R C II P S E F IIIII Tandem vs displaced duplication duplicated region is immediately adjacent T or located some distance even on different chromosome D Loop formed during meiosis is characteristic of duplication a b Normal chromosome A B C D E F C I a Chromosome with d u pl i cati o n A B C D E F E F G CI I I I Alignment in prophase of meiosis A B C D E F C I n II A B C D E F C ul D I I p 591 a Bar region Wild type ho BB b Heterozygous Bar 33 0 c Homozygous Bar 0 BB d Heterozygous I dOUb39e 3 BBD Wildtype chromosomes 1 Why does duplication alter phenotype Probably related to gene dosage Bar chromosomes Z 1 Genes are normal A B C W39Id type chromosome l l 1 Gene expressron L J J Embryo Interaction of gene products t quoti g i39 3 3 5 in 39 39 o o 397 I aw gt1 Normal development A B B C Mutant chromosome 1 l l 1 Gene expressron J J J T Interaction of gene products 0 0 Embryo Abnormal development Deletions can also be BAD Deletion of centromere leads to loss of the chromosome no segregation in meiosismitosis Loss of essential genes lethality if homozygous for loss Heterozygous deletions 1 Gene products Will be imbalanced 2 Allows recessive alleles on undeleted chromosome to be expressed pseudodominance 3 Some genes have to be present in two copies to produce enough gene product haploinsufficient ipym 14 457J 4 74 13 I Juepmnsuyoldeq s snaol 1191 Deletions lead to problems during chromosome pairing A B C D E F C I I D I I I Formation of deletion loop during pairing of homologs in prophase l E F A B C DI Si Appearance of homologous chromosomes during pairing Effects of some chromosome rearrangements in humans Type of Rearrangement Chromosome Duplication 4 short arm Duplication 4 long arm Duplication 7 long arm Duplication 9 short arm Deletion 5 short arm spaced Deletion 4 short arm Deletion 4 long arm Deletion 15 long arm obese Deletion 18 short arm Disorder Criduchat syndrome WolfHirschhorn syndrome PraderWilli syndrome Symptoms Small head short neck low hairline growth and mental retardation Small head sloping forehead hand abnormalities Delayed development asymmetry of the head fuzzy scalp small nose lowset ears Characteristic face variable mental retardation high and broad forehead hand abnormalities Small head distinctive cry widely syndrome eyes a round face mental retardation Small head with high forehead wide nose cleft lip and palate severe mental retardation Small head mild to moderate mental retardation cleft lip and palate hand and foot abnormalities Feeding difficulty at early age but becoming after 1 year of age mild to moderate mental retardation Round face large low setears mild to moderate mental retardation Inversions are another example of troubling chromosomal rearrangements Paracentric Inversion inversions that do not include the centromere Pericentric Inversions include the centromere Inversions gene order is changed can break a gene in two Regulation of genes is sometimes context dependent Inversion loop is characteristic present in meiosis A B C D E F C I CI I II D I Ill Paracentric InverSIO Formation of inversion loop Di I II 5252 J E s s a One wt chromosome one With paracentric inversion A B C D E F G I I u p 3qEEF d C D E D 1 EbDigcentric DI 99 nn quot cn II I l E D C r Anaphase E Cametes Normal nonrecombinant gamete annnnnnn Nonviable recombinant gametes C nunn E D I Nonrecombinant gamete with paracentric inversion nonviable Formation of inversion loop h Anaphase Lack essential genes 13 Crossing over within inversion i c C D E I 4 lD Il D39IlI J lIWIn Lacks centromere is lost d c F e E D C B A I x I D A n a p h a s e H e Gametes 39 Normal nonrecomblnant game e Nonviable recombinant gametes D C 22231212321222 D C E 4L39 Nonrecomblnant gamete with pericentric inversion Translocations movement between nonhomologous chromosomes Not crossing over bt homologous recombination Nonreciprocal translocation movement one way from one chromo to another Without equal exchange vs reciprocal translocation Results 1 Altered gene expression due to position effect eX Burkitt lymphoma 2 Break may occur in a gene d Nonreciprocal translocation of AB H c D Nonreciprocal E translocation K gt F L G Nonhomologous mogatgggnmosomes e Reciprocal translocation of AB and HI H H A I I B Reciprocgl I K translocatlon gt C L D M I F M E c F G Nonhomologous WEEDLQHTOSOmes P D 0 DD 3 F7 Translocations movement between nonhomologous chromosomes Robertsonian translocation translocation deletion Robertsonian translocation Metacentric l chromosome Fragment 1 Often lost Robertsonian translocation causes some forms of Down syndrome a Possible origin of a reciprocal translocation between two nonhomologous chromosomes 0 A N B C D K A O A V O B C MIN D Ki Translocations segregation in meiosis is a problem a Normal Translocated copy b l b Alternate segVacentl segregation Homologous ce romeres segregate to opposite poles k Adjacent2 segregation rare Anaphase I Kquot Alternate segregation I lAnaphase n Adjacenti segregation I Anaphase ll i llN Adjacent2 segregation rare I Anaphase ii i Y Viable gametes Y Nonviable gametes Aneuploidy changes in the Number of individual chromosomes Three reasons for this 1 Loss of chromosome Which has lost its centromere 2 Robertsonian translocation 3 Nondisjunction a Nondisjunction in meiosis I c Nondisjunction in mitosis Cametes Zygotes 5055 V mags q r moss I 1 mm U I lt mfg TEST 1 I 1 A OJ Mass k proliferation b Nondisjunction in meiosis ll Cametes Zygotes r M r MQD mm Q9 u U Trisomic Monosomic lt mg lt2nn lt2n w I l I Somatic clone Somatic clone Norma diploid of monosomic of trisomic j K 2 cells 214 1 cells 2n I Types of Aneuploidy Nullisomy loss of both members of homologous pairs 2n2 n haploid of chromosomes humans 2n46 Monosomy loss of a single chromosome 2n1 1 Turner sydrome is only example in humans Trisomy gain of a single chromosome 2n1 Tetrasomy gain of two homologous chromosomes 2n2 an organism With an extra copy of two different chromosome is not tetrasomy double trisomic Seed cases Jimson weed all different all different trisomics Trisomics Wild type Rolled Glossy Buckling Elongate Echinus Cocklebur Microcarpic Reduced KSpinach Poinsettia Globe Human Aneuploidies Sex chromosome aneuploides best tolerated aneuploidy XYY has very little impact due to lack of genetic info on Y Ex TurnerKlinefelter XOXXY Autosomal aneuploids smaller chromosomes 21 has 300 genes more tolerated Down syndrome 21 so 19 1 o 75 result from nondisjunction in mother an 2 21 22 O O 16 1 17 1 12 18 Ira 3 lI quot IIquot ic 4quot Cut quotuhquot of R t ml Human Aneuploidies 70 U I N Down syndrome per 1000 births I 01 Incidence of primary Down syndrome increases with maternal age 115 130 101000 31000 25 30 35 40 4S Maternal age years 50 Prophase I begins during fetal development Meiosis is arrested until just before ovulation Second meiotic division takes place prior to fusion of egg and sperm Sperm are turned over often Familial Down Syndrome translocation of a part of Chromosome 21 i 51 s l H 2 7 O o 9 I i U m I I is 9 9199 In an it v Runs in families parents have undergone a Robertsonian translocation 3amp0 0 1 12 l 3quot as 2 003 17 18 Familial Down Syndrome translocation of a part of Chromosome 21 P generation Normal parent 2H4 Gametogenesis Parent who is a translocation carrier 21 14 21 14 translocation l I Cametogenesisi 23 of live births Normal 13 of live births Aborted Embryo L l a l b l c D o G o lt9 14 2 2 14 14 212 14 14 2114 2 J i i i i i V v F1 generation K III III IIII III III III Translocation Normal Down Monosomy Trisomy Monosomy carrier syndrome 2 aborted i4 aborted i4 aborted Y j x 1 x Y J Other Autosomal Aneuploids Other Autosomal Aneuploids Trisomy 18 Edward Syndrome severe problems most die by age 1 Trisomy 13 Patau syndrome 50 die Within 1 month 95 die by age 3 Trisomy 8 Mosaic individuals can have normal life expectancy Uniparental Disomy Occurs when both chromosomes are inherited from one parent can result from trisomy that is resolved by loss of a chromosome during embryogenesis Trisomic zygote Gamete Compensatory N or mal rescue compl ementation U PD Mitotic error 30 Gametes D m w 6 C5 DH N Disomy Trisomy U PD Monosomy Disomy Nondisjunction Nondisiunction Mitotic gm duplication recombination Duplication H U D 3 E 2 EB E O 0 UPD UPD UPD UPD Pa t39a39 UPD 1 000000 spontaneous abortions 1 50000 chromosome abnormalities 75000 conceptions I u v 850000 live births l v v w 833000 17000 children perinatal deaths v 5165 chromosome abnormalities 1183 autosomal trisomics 758 balanced quot Robertsonian translocations 758 balanced 39 reciprocal translocations 117 inversions 500 unbalanced 1849 sex chromosome lt 1427 males aneuploids 422 females 42 trisomy 13 100 trisomy 18 1041 trisomy 21 structural aberrations 39000 trisomics 3510 trisomy 21 13500 X0 12750 triploids 4500 tetraploids 5250 others Chromosome Mosaicism An organism can have normal tissues and tissues that have chromosome abnormalities that result from nondisjuctions Gynandromorph is both sexes XX and X0 S2 phenotype 8 phenotype XX X0 I f i r I f Red eye 39 White eye Wildtype Miniature wing Wing Polyploidy How do these arise 1 Errors in meiosis 2 Events at fertilization 3 Errors in mitosis following fertilization Dispermy is one at Fertilization mech simultaneous fertilization of egg with two sperm Humans Triploidy is most common found in 1518 of spontaneous abortions 75 have two sets of paternal chromosomes dispermy 1 of all conceptions are triploid 99 die before birth 1 in 10000 live births fatal shortly after birth Polyploidy autopolyploidy all chromosome sets are from same species allopolyploidy chromosome sets are from different species a Autopolyploidy through mitosis MITOSIS 7 Y k e cation i Separation of gt 5 Nondisjunction gt 21 p a chromatids lt 3 no cell division 1 1 Diploid 217 early Autotetraolloid kembryonic cell 4n ce b Autopolyploidy through meiosis Cametes Zygotes KMEIOSISI MEIOSIS ll K lill illilllldis mw ltzf a 2quot I Diploid 2n 2n J k Tri 3n Problems with meiosis when polyploid KMEIOSISI MEIOSis ll First meiotic cell division Anaphase Cametes a H 2quot r D gt Pairing of two of three homologous chromosomes 1 m m inquot H L l cell homologous chromosomes 3n Chromosomes j K absent l 4quot til lil No pairing Usually results in sterility used in agriculture seedless fruits are often sterile polyploids tend to have larger fruits too more chromosomes the larger the fruit Alloploidy occurs as a result of hybridization followed by chromosomes doubling G generation F1 generation Species SPECiES Hybrid ellllll illllll CC H H A B C C H 2n 6 2n 6 G t l Nondisjunction at an early mitotic CametogeneSIs cell lelSlon J EYE Nonviable B H gametes V Allotetraploid AABBCCCCHHII 4n12 Cametogenesus Cametes Species 2 Allopolyploids can occur as a result of hybridization followed by chromosomes doub ng anlold garnetes Otplongamotu u 39 I will GURE Allopolyploids an Form New Species Unreduoed gamete Unreduoed gamete with 4 chromosomes with 7 chromosomes reduced trom 2n to n Hybrid with Viable fertile IIde f 7chromoeomee allopolyptold 39 Melotlc error quot4 chromosome f 39 numbernot 39 39 L I Normal gamete n 3 39 gt x I Normal gamete 39 l y n a 3 V w Copyrtgm 0 Pearson Education Inc publishing as Benjamin Cummings Modern Wheat resulted from allopolyploidy P generation Einkorn wheat Wild grass W m k IiiW an Trltlcmonoccum Trltlcuwmwgearsu W 39 A quot Jinxf J 3 00 0 M f I H 1 j a r HM Ira u 39 9 w M I I 39 g 39 quot 39 39 r39 I 4 I It I Iquot vquot rquot I I u 1 quot 39139 t a 39 v y 39 a 1quot V Vquot 33 I a 39 39I Iquot I 8 g 39 3399 I w 1 x I 394 39 n 3951 s Ill 3 e 39939 s e 1 26 03 J u f o N 9 6 n39 0 Ilf U VIquot I Genome AA Genome BB 2n14 2n14 Gametes F1 generation quot Hybrid Genome AB 2n 14 Mitotic nondisjunction amp II I l EmimgellrQv egEV Wild grass Triticum39fturgidum Triticum itauschi Genome DD 2n 14 F2 generation I I I Hybrid Genome ABD 3n 2 Mitotic nondisjunction Breed We Trittmativum mm Genome AABBDD 6n 42 Table 92 Examples of polyploid crop plants Plant Type of Polyploidy Ploidy Chromosome Number Potato Autopolyploid 4n 48 Banana Autopolyploid 3n 33 Peanut Autopolyploid 4n 40 Sweet potato Autopolyploid 6n 90 Tobacco Allopolyploid 4n 48 Cotton Allopolyploid 4n 52 Wheat Allopolyploid 6n 42 Oats Allopolyploid Gr 42 Sugar cane Allopolyploid 8n 80 Strawberry Allopolyploid 8n 56 Source After F C Elliot Plant Breeding and Cytogenetics New York McCrawHill 1958 Fragile Sites and Human Syndromes lt fragile site fragile X syndrome p Fragile site prone to breaking Fragile X syndrome 1 in 2000 males 1 in 4000 females most common form of inherited mental impairment results from increase in number of trinucleotide repeats NOTE Breakage is not cause of disease Males exhibit elongated face large ears enlarged testes mental impairmentusually after puberty Why Fragile Sites and Human Syndromes S39Uirlreraluegrl 3 L39niranslaire Ali Hera3n Fn39isf e FMSE1 Ef39 j r l n quotl i h n h i JLL i quot39 39 I quot quot quot 5 Hilaheses IE Slarll nrlnn 7 He39llah Lei35hrquot ring guanine re 1 I 1 II II39ilrzll39i quotl I relrlnler 1 I g Millll39fl 17mm a La I u 14H Hrsrnul quot n Irai e ul iml In ll learni 391 M E39 F i quot 39 F39relnnluirliznni 39 J L g I hear lrwjuei ljunnn39nai I EI39Eln39i Emquot Marketingi I rrll1lelua39r Fa lelhsrlmien r39l 3 Fillniwu Figure 3 Trinuelehiide eepaneihn reepenaihle fer fragile 3 eyrndreme lies in an uneereeeed earl el lhe H linlred gene FMFH The gene i leelf Hep diuidee iia he irrle 1 exene epre ever 33 kileheeee He I39irel an Iae1 eeene inelue regiene 1rerreeri inie meeeenger FINE that are l39iiEli repreeented in lane Iinal 1rerrala1ed relein In lurn Ihe unirenelaled regihn in eeen 1 ineluee a eeuerree ref 11313 reele hetlern Nermelly lhe heel ia phlyrnerphie ranging Irem Tquot 1e 52 repelilihna The example ehmun ie Ihe mne l eammenq Irri lh 33 In a ren ru laliienE Ihe numher ie ll in EDIE the example has QED In a lull mulalihn 1he nun39l her is alrneali elmraga aeeer el hundre Ihe E39EEEITI ple hea TED When Ihe nun39l her eeide 333 Ihe en lie reien ie hypemle llrryla led ineeilq reeeiein a meflrhyl greupa ai the I in each dinueleeliide alhng he lh atrande e l Ihe DINA deu hle helix The gene39e rerne ler ie exeeiirraleljl an ihe gene henemee eilenli ner15 i1 and near FltPH marl5 ihe leeaiiene ef ihree pelyrnerphien39le Trinucleotide expansion and Premutation lead to methylation and blockage of transcription fragility is related to length of repeat region Genetic anticipation number of repeats increases in future generations causing symptoms to be worse Fragile site breaks are very common in some tumor cells Table 93 Different types of chromosome mutations Chromosome Mutation Chromosome rearrangement Chromosome duplication Chromosome Inversion Paracentric inversion Pericentric inversion Translocation Nonreciprocal translocation Reciprocal translocation Aneuploidy Nullisomy Monosomy Trisomy Tetrasomy Polyploidy Autopolyploidy Allopolyploidy Definition Change in chromosome structure Duplication of a chromosome segment Deletion of a chromosome segment Chromosome segment inverted I80 degrees Inversion that does not include the centromere in the inverted region Inversion that includes the centromere in the inverted region Movement of a chromosome segment to a nonhomologous chromosome or region of the same chromosome Movement of a chromosome segment to a nonhomologous chromosome or region of the same chromosome without reciprocal exchange Exchange between segments of nonhomologous chromosomes or regions of the same chromosome Change in number of individual chromosomes Loss of both members of a homologous pair Loss of one member of a homologous pair Gain of one chromosome resulting in three homologous chromosomes Gain of two homologous chromosomes resulting in four homologous chromosomes Addition of entire chromosome sets Polyploidy in which extra chromosome sets are derived from the same species Polyploidy in which extra chromosome sets are derived from two or more species Chromosome 4 differs in humans and chimps by inversion Centromere Human chromosome 4 II II II IIIIIIIIIII IIIII J Y Pericentric D inversion Chimpanzee chromosome 4 r A Robertsonian translocation and Evolution Human chromosome 2 4 IIIIIIIIIII l IIlIIIIIlIII 6 Chromosomes Chimpanzee chromosomes Gorilla chromosomes II II quotIII IllIII IID Orangutan chromosomes II IIIIIIIIIIIIIIID HI IIIIIIIII 891110801110an 817 The only major structural differences 1 a number of pericentric and paracentric inversions 2 the recent fusion of two chromosomes to form human chromosome 2 3 a reciprocal translocation between the gorilla chromosomes Which correspond to human chromosomes 5 and 17 90100 identity at sequence level Duplieations in Evolution Gene Redundancy and ampli cation Gene Families Glx ihl H1 gene elue ter J r L Eehin cl meter Spacer Diem is neneeding Jere between gene family H39IEIETI39IlleaI39S E In D m D a 3 W Mfg 29m Feeudeige l Peeudegenee are family membere that le net needle ler Funeli nal mRHm er preteineh ii M a 12 Ge a 39 we1 e i E I 1 000000 spontaneous abortions 1 50000 chromosome abnormalities 75000 conceptions I u v 850000 live births l v v w 833000 17000 children perinatal deaths v 5165 chromosome abnormalities 1183 autosomal trisomics 758 balanced quot Robertsonian translocations 758 balanced 39 reciprocal translocations 117 inversions 500 unbalanced 1849 sex chromosome lt 1427 males aneuploids 422 females 42 trisomy 13 100 trisomy 18 1041 trisomy 21 structural aberrations 39000 trisomics 3510 trisomy 21 13500 X0 12750 triploids 4500 tetraploids 5250 others Alfred Henry Sturtevant student of TH Morgan Morgan suggested that genes on same chromosome segregated together also those closely linked were rarely subject to recomb 1911 Sturtevant generated first map of chromosome based on recombination frequency Sturtevant s symbols B C P R M X chromosome locations 00 10 307 337 576 Modem symbols y w v m r I Yellow White Vermilion Miniature Rudimentary body eyes eyes wings wings Review Principle of segregation each diploid individual possesses two alleles that separated in meiosis one allele to each gamete each allele is at the same position on a homologous chromosome Principle of Independent assortment two alleles separate independently of alleles at other loci Chromosome theory of heredity Sutton genes are found on chromosomes P generation AAIBB gtlt aalbb Camete formation Camete formation i i Cametes G generation Au Eh I Gamete formation A i l Cametes HJ Original combinations of New combinations of alleles nonrecombinant alleles recombinant gametes gametes Conclusion Through recombination gametes contain new combinations of alleles KP generation Homozygous strains Purple flowers Red flowers long pollen round pollen L quot J Fertilization KFI generation Purple flowers long pollen Selffertilization FF generation Purple flowers long pollen r 2 generation l f A l 28439 21 55 Purple flowers Purple flowers Red flowers Red flowers long pollen round pollen long pollen round pollen l Conclusion F2 progeny do not appear in the 9331 ratio expected with independent assortment Linked genes those that are close together on same chromosome travel together during meiosis do not usually sort independently I Relationship baween modem genetic terminology and character pants used by Mendel Charade pair used by Alleles in Located in Mendel modem terminology chromosome Seed colom yellowamen la I Seed coat and owers colouredwhile Aa I Mature pods smomh expandedwrinkled indented Vv 4 ln from leaf axilsumbcllalc in top of plant Fafa 4 Plant height gt luvaround 05 m LeIe 4 Don39t pods greenyellow Gp gp 5 Mature seeds 7 smoothwrinkled Rr Leads to switching of genes from one homologous chromosome to another responsible for recombination Late Prophase Metaphase Anaphase Cro sing Recombinant K chromosomes zm Genes t hat are normally linked now sort independently Metaphase MR Anaphase m gt Gametes Gametes I Prvg Parental chromosomes Crossover between chromatids Meiosis Crossover chromosomes a If genes are completely linked no crossing over Normal leaves tall l Gamete formation I v2 v2 Non recombinant Mottled leaves dwarf I Gamete formation gametes L L k j i Normal Mottled leaves tall leaves dwarf All nonrecombinant progeny nonrecombina nt progenyare produced lConclusion With complete linkage only b If genes assort independently Normal leaves tall Mottled leaves dwarf leaves tall I4 Mde 394 mmdd L P Nonrecombinant progeny X gamete iormation l Gamete formation V4 4394 Nonrecombinant Recombinant gametes gametes I L L L L Fertilization L j Normal Mottled vNormal Mottled leaves dwarf leaves dwarf leaves tall Recombinant progeny Conclusion With independent assortment 14 progeny are recombinant llzarenot Prophase I homologous chromosomes pair a No cro sing over EBp B 31 W B3D m m 1399 m b Crossing over ap Nonrecombinant 5315 Recombinant may Recombinant m Nonrecombinant Single crossover leads to half Prophase I crossing over can occur recombinant half nonrecombinant Normal leavestaH gtlt Gamete formation A f No crossing Crossing over over m Mottled leaves dwarf Gamete formation l ill Nonrecombinant Nonrecombinant Recombinant gameteslOO gametes 50 gametes 50 L L J J L L Fertilization l Normal Mottled Normal Mottled leaves tall leaves dwarf leaves dwarf leaves tall u 3 Progeny t number 8 7 1 Y Nonrecombinant Recombinant progeny progeny Conclusion With linked genes and some crossing over nonrecombinant progeny are predominate 9 Cross B 0739 Q Cross A d y W y W a x E t y w yellow white wild type S d V W y w E lt y w wild type yellow white Parental Recombinant types 995 types 05 y W y W E L V k r wild type white y W y w m t yellow white yellow y W y W E y W y W wild type white y W y w a y W y w yellow white yellow 2012 Pearson Education Inc w m w m 3 x P1 E L w m I white miniature wild type 9 o w m w m F1 m w m wild type white miniature Parental Recombinant types 655 types 345 w m w m a a F wild type miniature 2 males W m W m O white miniature white wJr m r w m E a w m w m F wild type miniature 2 females W m W m g u w m w m white miniature white Linkage mapping Alfred H Stewart postulated that frequency of recombination could be used to determine the physical distance separating two genes on a chromosome Alfred Henry Sturtevant P Iutu numln39 u C JIJ 5w II39 No 13 I High recombination I I a b I I3 I LoW recombination I a b Parental Recombinant types 995 types 05 y W y W E m L l t wild type white y W y w Ea k yellow white yellow y W y W a n y W y w wild type white y W y w Ea y W y w yellow white yellow 2012 Pearson Education Inc males I2 females Parental Recombinant types 655 types 345 w m w m H m wild type miniature w m w m m white miniature white wquot m r w r m H n w m w m wild type miniature w m w m m w m w m white miniature white 2012 Pearson Education Inc Harriet Creighton and Barbara McClintock translocated segment Colored starchy Colorless starchy Colorless waxy Case ll Colored starchy 2012 Pearson Education Inc Normal Mottled Normal Mottled leaves tall leaves dwarf leaves dwarf leaves tall u 3 Progeny t number 8 7 1 Y Nonrecombinant Recombinant progeny progeny Conclusion With linked genes and some crossing over nonrecombinant progeny are predominate Recombination Frequency Recombination Frequency of recomb progeny total of progeny x 100 87 875355 x 100 12 Sturtevant s symbols B C P R M X chromosome locations 00 10 307 337 576 Modem symbols y w v m r n I Yellow White Vermilion Miniature Rudimentary body eyes eyes wings wings Coupling and Repulsion a Alleles in coupling configuration b Alleles in repulsion F N F W Green thorax Purple thorax Green thorax Purple thorax brown puparium black puparium brown puparium black puparium Testcross V a X 7 plb Gamete formation l I Gamete formation Gamete formation l Gamete formation l H H l H H l Nonrecombinant Recombinant Nonrecombinant Recombinant gametes gametes gametes gametes L L L L L L L L v n Fertilization K j k j 4 Green thorax Purple thorax Green thorax Purple thoraQ K Green thorax Purple thorax Green thorax Purple thoraQ brown black black brown black brown brown black puparium puparium puparium puparium puparium puparium puparium puparium Progeny 40 Progeny 40 number number Nonrecovmbinant Recomvbinant Nonrecovmbinant Recornrbinant progeny progeny progeny progeny Conclusion The phenotypes of the offspring are the same but their numbers differ depending on whether alleles are in coupling configuration or in repulsion Coupling cis Wild type alleles on one chromosomemutant on the other Repulsion trans each chromosome has one wt and one mutant Independent Assortment Linkage and Crossing Over Genes may be 1 On different chromosomes independent assortment combine randomly AaBb two different nonrecombinant gametes AB ab two different recombinant gametes Ab aB 222 923 33 32 Gametes Independent Assortment Linkage and Crossing Over Genes may be 2 Completely linked on same chromosome close together so crossing over is Age A a a rare Independent Assortment Linkage and Crossing Over Genes may be 3 Incomplete linkage genes on same chromosome but some distance apart allows some recombination B B Nonsister b chromatids 09 gt25 Crossover Gametes Crossover gamete Independent Assortment Linkage and Crossing Over Genes may be 1 On different chromosomes independent assortment combine randomly AaBb two different nonrecombinant gametes AB ab two different recombinant gametes Ab aB 2 Completely linked on same chromosome close together so crossing over is rare 3 Incomplete linkage genes on same chromosome but some distance apart allows some recombination Interchromosomal recombination between genes on different chromosomes arises from independent assortment in Anaphase I of meiosis Intrachromosomal recombination between genes on same chromosome crossing over in prophase I of meiosis Recombination Frequency Background smooth fruit t is recessive to warty fruit T Glossy fruit d is recessive to dull fruit D Recombination freq is 16 for the two genes can we use this info in predicting the proportion of progeny in a test cross Warty dull fruit Smooth glossy fruit Testcross Camete formation Him 1 Nonrecombinant Recombinant Nonrecombinant gametes Predicted 042 042 frequency L L Fertilizatlon k Since recombination freq 16 total proportion of recombinants must be 16 Predicted frequency Warty dullfruit Smooth loss fruit 9 y t d t d Warty glossyfrurt T d t d Smooth dullfruit t D t d of progeny 042 X 100 042 Non gtrecombinant 042 x 100 progeny 042 J 008 x 100 008 gt Recombinant 008 X 100 pmgeny 008 Gene Mapping with Recombinant Frequencies Genetic maps use recombination frequencies to make chromosome maps Distances are in terms of Map units 1 recombination frequency aka centimorgans cM Physical Maps chromosome maps based on physical distances base pairs A to B distance is 5 cM B to C distance is 10 cM A to C distance is 15 cM U Is there a Different combination Gene Mapping with Recombinant Frequencies Remember 1 Recombination frequency cannot be gt50 for two genes 2 50 is the frequency of recombination for genes on different chromosomes so impossible to discern between two genes that are far apart on the same chromosome and those on different chromosomes 3 Genes that are far apart can undergo DOUBLE crossovers so it appears that crossover never occurred Relationsth between modern gcnctic tcrmtnoloxy and character path used by Mendel Character patr used by Allclcs tn LUL39dlCd in Mendel modem It tmnology chromosome Seed colour yellow green l a l Sccd coat and owers coloured white 4 a l Mature pods smooth cxpandcdmmkkd tndcntcd V v 4 ln orcwcnocs from leaf axils umbcllatc In top of plant I dfa 4 Plant height gt tm around 05 m Lrlc 4 Unripc pods green 39cllow Gp gp 5 Mature seeds smoothwrinkled R r J Using TwoPoint Testcrosses to make a Genetic Map TWOpoint testeross testcross between two genes four genes abcd Crosses a and b 50 recomb Freq a and e 50 a and d 50 bandeZO b and d 10 e and d 28 Linkage groups Distant markers can be tied together by intermediate markers CM 15 1O 15 1O 20 NeitherA nor B would be linked to F in a 2 point cross Intermediate markers allow a linkage group to span greater than 500M distance Threepoint crosses are more ef cient than Twopoint crosses Why 1 Order of genes can be established in a single cross 2 Double crossovers can be detected providing more info Centromere n m I 13 gt Pair of homologous chromosomes 1 l a Single crossover b Single crossover c Double between A and B between B and C crossover ElEDD EEEI 53535 5 53 53 I I D a V b b a 553 EEI 1 E B 53 m ED Double crossover yields recombinant chromosomes With altered middle gene 3 point test cross AABBCC x aabbcc J AaBch x aabbcc ABC 0 Parental abc O 473 NCO 33C 1 Recombinant Abc 1 quot SCO ABC 1 Recombinant abC 1 SCO AbC 2 1 2 Recombinant ch 2 1 DCO OOO 3 point test cross ABC 0 479 952 abc O 473 aBC 1 15 28 Abc 1 13 ABc 1 9 18 abC 1 9 2 1 2 a 2 1 1 000 A B C I I I I I I or C B A 3 point test cross C O 479 952 abc O 473 aBC 1 15 28 Abc 1 13 ABc 1 9 18 abC 1 9 AbC 2 1 2 ch 2 1 1 000 The percentage of recombinants between A and B 281 000 028 21000 002 03 3 8 point test cross C 0 479 952 abc 0 473 aBC 1 15 28 Abc 1 13 ABc 1 9 18 abC 1 9 AbC 2 1 2 ch 2 1 1 000 The percentage of recombinants between B and C 181000 018 21000 002 02 2 3 point test cross C O 479 952 abc O 473 aBC 1 15 28 Abc 1 13 ABc 1 9 18 abC 1 9 AbC 2 1 2 ch 2 1 1 000 The percentage of recombinants between A and C 28181000 046 41000 004 05 5 3 point test cross ABC O 479 952 abc O 473 aBC 1 15 28 Abc 1 13 ABc 1 9 18 abC 1 9 AbC 2 1 2 ch 2 1 1 OOO 50M lt gt A B C I I I I I I 30M 20M What is the order of these three genes Recessive mutations st scarlet eye mutation e ebony body color ss spineless small bristles Wild type Scarlet ebony spineless gtlt st e 55 st 6 55 l J Y Testcross I j i 1 Score progeny for mutations Progeny genotype Progeny number Progeny phenotype 5t e 55 stess gt gt 39 quot Wild type 283 st e 85 y All mutant 278 St SS Ebony spineless 50 I st e 53 Scarlet 52 Ebony 43 Scarlet 4 spineless l Total 755 l Nonrecombinants most numerous Double crossover least numerous phenotypes bc of low probability of double event 2 Consider possible gene order Progeny Progeny Progeny genotype phenotype number 5t 6 55 J Wild type 283 st e 55 7 st ess st e 55 39 All mutant 278 st 6 ss st e 55 st e 55 w Ebony spineless 50 st e 55 stJr e 53 st e 55 quot j Scarlet 52 st e 55 quot st e Lss st e ss Vt Spineless 5 5t e 55 quot39N st e4r 55 st e 55 p quot39quot39quot j Scarlet ebony 3 5t 6 55 st 6 33 st 8 55 4 Ebony 43 st e 55 st 6 53 st e ss M W 4 1 st 6 55 f spineless st e ss Total 755 e st ss st e ss st ss e Easiest to figure out by comparing non recombinants to double crossovers st e ss st The second set of non to double crossovers e ss st e ss st e ss Why don t we group other waynonrecomb and double crossovers 2 Which changes must be in the middle SS e st 55 The pOSSIble orders st e 55 st 55 e st e 5er SH e 55 st st e 55 st e 5er Wild type Scarlet ebony spineless gtlt st 55 e st 55 e st 55 e l J Y Testcross genorype pnenOIype numDer st 35 e Wild type 283 st 55 e st 55 e Scarlet ebony st 55 e spineless st 55 e ll Spineless 50 st 55 e ebony st 55 e Scarlet 52 st 55 e st 55 e Ebony st 55 e W Scarlet 4 m spineless st 55 2 Spineless 5 st 55 e st 55 e L Scarlet 3 st 55 e Ebony Total 755 J Calculating Recombination Frequency or Map Distances Add up all recombinant progeny divide by total number of progeny X 100 EX What is the map distance between eye color st and bristle ss Total progeny 755 st ss e st ss e 50 st ss 6 52 st ss e 5 st ss e 3 110 Calculating Recombination Frequency or Map Distances For sse again add up all recombinant progeny divide by total number of progeny X 100 st ss e 43 st 55 6 41 st ss e 5 92 st sse 3 97755 x 100 122 or 122 mu How about Recombination Freq Between st and e Add 146 122 268 mu How do our observed numbers compare to expected The probability of double cross over occurring can be calculated based on probability of the two single crossovers multiplied together st ss e Exp Freq RF1 X RFZ X observations stss 0146 sse 0122 0146 X 0122 00178 00178 X 755 134 predicted double crossovers We only observed 8 double crossovers What happened We have assumed that one crossover does not in uence another OFTEN WRONG Interference Interference once one crossing over occurs the chromosome now avoids adding any more crossing over near that interferes Interference and Coef cient of Coincidence COC of observed double crossovers of expected double crossovers 8 134 06 Interference 1COC 04 this means that 40 of doule crossover progeny expected Will not be observed because of interference If interference 1 how many double crossovers Will you get You saW no cross over events If interference 0 you would say you observed the number of double crossovers that you expected a Twostrand double exchange No detectable recombinants 2012 Pearson Education Inc 393 50 4O Theoretical Actual 20 10 Recombinant chromatids l l 10 20 30 4O 50 6O 7O 80 Map distance map units Linkage mapping 1 recombination 1 centiMorgan Female map 15X male map ch le human ch 2Mb mice 0 o 9 o Recombmatlon hot spots areas Where recomblnatlon occurs more often than expected Colinear maps 0 4 vWF o1o 011 PR83 1 o O 01azfQRB1 quot00 on R82 o42 133 132 131 123 F 122 105 KRASZ 121 ooo 112 L16 01252 111 quoton 1 1 131 COLZA 39oo9 12 138 ELA 2 MM ooo 146D124 o 03 131 149 PYNHIF quot001 132 150 01256 133 14 O29 15 211 q 212 191 39 01258 213 o 26 22 23 228 T 01257 241 242 O22 243 24 253 4 PAH a D 6 OOO oooooop O23 PRBJ 4 o02 PRB1 o 03 Paez 020 KRAS2 oo4 232 quotquotquotquotquotquot quot 39 5 LA1 JpSCMM122quot39g39g 25 o02 012562quotigt 7NH1 5 39 14 gt 01258 quot012 gt 01257 o 009 PAH Genetic Map of Drosophila Chromosomes 7 5 2 I a Chromosome 1 X Yellow body quotScute bristles White eyes Facet eyes Echinus eyes x Ruby eyes I III lllllV lzp 137 Crossveinless wings 200 Cut wings 210 Singed bristles 277 quotLozenge eyes 330 Vermilion eyes 36 Miniature wings 430 Sabe body 440 Garnet eyes 567 I Forked bristles 570 3 1 Bar eyes 595 Fused veins 625 Carnation eyes 660 Bobbed hairs 1005 l04539 107039quot h Chromosome 2 Net veins iAristaless antenna Star eyes I ll quot I u I l l I l i quotHeldout wings quotDumpy wings 39 Clot eyes Black body Reduced bristles Purple eyes Short bristles Light eyes Cinnabar eyes Scabrous eyes Vestigial wings I 4 Lobe eyes Curved wings Plexus wings Brown eyes Speck body a 00 02quot l92 260quot 265quot 1007quot l062quot39 11 II ll 1 ll I II I I II I ll u l l i Chromosome 3 Roughoid eyes Veinlet veins Javelin bristles Sepia eyes Hairy body Dichaete bristles a Thread arista Scarlet eyes Pink eyes Curled wings Stubble bristles Spineless bristles Bithorax body Q Stripe body Class eyes Delta veins Hairless bristles Ebony eyes Cardinal eyes I H II I Rough eyes Claret eyes Minute bristles 00quot Chromosome 4 e x Eyeless Bent wing leubitus veins Shaven hairs Crooveless scutellum We are not limited to mapping physical traits we can use molecular markers still based on segregation of two or more markers Molecular Markers Restriction fragment length polymorphism RFLP Changes in DNA sequence that modify restriction enzyme recognition sites Variable number of tandem repeats VNTR Differences in copy number SSLP Minisatellite Microsatellite Single nucleotide polymorphism SNP A single base change N EIIIIIAL DISEASE N m DISEASE N m Me Ieetliethn sin i E Diwt mi 5 39 Muhiium hie339s Gel eleeirep heresis Seu tern hlet Inheritance ef Parents RFLP markers l S ings AA 1 A A3 A3 aa A3 AA Mierosatellite markers Di tri tetra nucleotide repeats f H CA CA CA CA CA CA CA CA CA CA CA CA CA CA CA CA CA CA r H CTG CTG CTG CTG CTG CTG CTG CTG CTG CTG CTG CTG f H GAAA GAAA GAAA GAAA GAAA GAAA GAAA GAAA GAAA GAAA Mierosatellite markers Polymorphic repeats of 24 base pairs Codominant Complementary I priming region I Tetranueleotide repeat 116 GAAA Grandparent 13 Pare nt5 35 15 J Ehildren 25 25 12 5 12 139r39 5 1 i i i i i 2 i i i i It It 3 i 4 i 5 i i i i i i i T i i i i i H mm mm m m 393 A 115 55 E39Ei i g E55 91 1 m a 7 1m IE El 5m 15 m 31quot 1M 1 iEIT I m 91 mi 13 V 1 251 539539 21 35inI 55 1E Izil 1213 ail EH n aill1 M 15 huhh manA humuhunmmmmd ML uhn munmmmh Study Guide Exam 11 end of 47 I Ch 4 cont a Sex chromosomes Morgan first to explain sexlinked inheritance he had found that some traits were associated with one sex or the other i ii iii X Linked recessive traits Mom passes it to both sons and daughters Father passes Y to sons so it s more common in sons Daughters have a chance to have it suppressed by addition of another X males affected more gt females Affected sons are usually born to unaffected mothers thus the trait skips generations X linked Dominant traits heterozygote females pass the trait to half of their sons and half of their daughters The affected males pass to all daughters and none to sons Expect to see it in every generation until it stops then it s gone Females affected more gt males Y linked traits appear only in males pass male to male Always shown because it s on the Y and there is only one Y in males Does not skip generations b Sex in uencedlimited i Sex in uenced determined by autosomal genes but expressed differently in males and females So the same gene autosomal same alleles can be present but phenotypic expression is different depending on male or female The sex chromosomes in uence how the autosomes are expressed One reason for the different phenotype is because different hormones are present for males and females 1 Example of a sex in uenced trait is pattern baldness C ii Imprinting ii a Men require only one bald allele while females require two Allele is expressed weakly in females Sex limited characteristics characteristics that are determined by autosomal genes but expressed ONLY in one sex zero penetrance in other sex Genomic imprinting occurs with autosomal genes males and females contribute equal number of genes but expression is affected by parental origin Genomic imprinting is the epigenetic phenomenon by which certain genes are expressed in a parentoforiginspecific manner If the allele inherited from the father is imprinted it is thereby silenced and only the allele from the mother is expressed 1 Example PraderWilli syndrome Angelman syndrome a PWS small handsfeet short stature mental retardation frequently become obese due to increased appetite b Always INHERITED from father c PWS is caused by the absence of segment 1113 on the long arm of the paternally derived chromosome 15 In 7080 of PWS cases the region is missing due to a deletion d BUT in others no deletion detected both copies of 15 from mom uniparental disomy 2 Example Angelman syndrome a Uncontrollable puppetlike movements laughter AS b 50 have deletion in 15 like PWS c If not deleted both copies come from father d SO for normal development need one copy from each parent 3 IMPRINTING DOES NOT AFFECT ALL GENES a Methylation of DNA epigenetic modifications may be at work b Epigenetics genome modifications that cause functional differences but do not change the nucleotide sequence d Cytoplasmic Inheritance there are genes located in the cytoplasm chloroplasts and mitochondria i A zygote inherits nuclear genes from both parents but almost all of the cytoplasmic genes come from the mother because the egg is huge and the sperm is small in the sperm the tail region has the mitochondria but the tail is not part of fusion so it s not used ii So with cytoplasmic inheritance the affect female passes it to all children but the males do not pass the trait to children e Maternal effect i The PHENOTYPE is determined by GENOTYPE of mother ii The genes are inherited from both parents not cytoplasmic inheritance but the offspring s phenotype is determined by the genotype of the mother So then the offspring s children will have a phenotype that matches the genotype of the mother Table 55 Sex influences on heredity Genetic Phenomenon Phenotype determined by Sex linked characteristic Genes located on the sex chromosome Sexinfluenced characteristic Genes on autosomal chromosomes that are more readily expressed in one sex Sexlimited characteristic Autosomal genes whose expression is limited to one sex Genetic maternal effect Nuclear genotype of the maternal parent Cytoplasmic inheritance Cytoplasmic genes which are usually inherited entirely from only one parent Genomic imprinting Genes whose expression is affected by the sex of the transmitting parent Table 55 GeneticsA Conceptual Approach Fourth Edition 2012 W H Freeman and Company 11 Ch 5 a Sex determination systems Mechanisms 1 Chromosomal Sexdetermining system the XY or XX determines sex a Heterogametic sex the sex that produces two different gametes b Homogametic sex the sex that produces identical gametes c Sometimes insects do not have sex chromosomes making them male and haploid 2 Genetic Sexdetermining system similar to chromosomal sex determining since genes drive the sex determination Genes determine the sex of an individual No obvious difference in chromosomes no sex chromosome Found in some protozoans and plants 3 Environmental Sexdetermining system environmental conditions determine the embryonic development into male or female a Example common slipper limpet if it develops alone it s a female But if another embryo comes to it and attaches then it develops as a male b Example alligators warm temperatures male Cool temp females b Important people i Henking noticed that male insects had a strange body in nuclei X body ii McClung said X body chromosome noticed how female grasshopper cells had 1 more chromosome than males iii Stevens and Wilson said female grasshoppers have 2 X chromosomes 1 Also noted how males had a smaller chromosome Discovered X and Y separated into different sperm cells while egg cells all get single X c Nondisjunction the failure of these chromosomes to separate properly from each other d i Discovered by Morgan and his student Bridges He bred ies He found that all but 3 had red eyes the 3 random had white Bridges hypothesized that the X chromosomes failed to separate in anaphase 1 because the occurrence of white over red occurred too often to be a mutation ii Also the sex of Drosophila ies is determined by the ratio of autosomes to the number of X Syndromes related to sex chromosome abnormalities i Turner Syndrome 45 chromsomes X 1 Femalesno puberty low hairline folds of skin on neck may have cognitive impairment sterile ii Klinefelter Syndrome 47 chromosomes XXY 1 Males small testes breasts reduced facial hair at least 1 Y and multiple X often sterile may have mild cognitive impairment Often undiagnosed if XXY find out if they try to have kids Extra Ys don t really matter but extra Xs led to worse phenotype iii PolyX females 1 Typically it s triploXsyndrome XXX which is normal almost Tall thin can be fertile normal intelligence 2 But with gt3 X s there leads to an increased chance of sterile defect in anatomy cognitive impairments SRY gene Sex determining region Y found in all XX males but not in XY females Triggers the development of gonads into testes Found in mice Androgen insensitivity syndrome alternative to SRY gene but for women These women with this syndrome have female sexual characteristic but not uterus or ovaries Testes are found in abdominal cavity These women are XY g Pseudo autosomal regions allow the chromosomes to line up into little bits of homology so that it can split eventually h Dosage compensation how to deal with multiple Xs i ii iii iv Dosage compensation is monitored by Barr bodies they function to ensure that males and females have equal quotdosesquot of the genes on the X chromosome Barr discovered the Barr body has a darkly stained body in the nuclei of cat cells Lyon proposed Barr body was inactive X chromosome Lyon Hypothesis X Inactivation females heterozygous at X loci will express one allele over the other in a given cell Females are MOSAIC for expression of X linked genes Barr bodies only present in females All but one X chromosome is inactivated in every human somatic cell Barr bodies are unrelated to sex determination Only deals with inactivation of X chromosome which occurs early in development vi Mosaic denotes the presence of 2 or more populations of cells with different genotypes in one individual who has developed from a single fertilized egg can be due to nondisjunction 111 Ch 6 a Karyotype display of a complete set of chromosomes b Duplications extradouble genes i Types 1 Tandem duplication duplicated region is immediately adjacent 2 Displaced duplication the duplicated region is located some distance away or even on a different chromosome ii Consequences 1 Can lead to a loop being formed during meiosis prophase 1 2 The duplication alters phenotype probably because of the unequal gene dosage c Deletions i Types 1 Can be deletion of single parts of a gene can form a loop which leads to problems during chromosome pairing 2 Or it could be a deletion that includes the centromere and if that s the case then the entire chromosome is loss because without a centromere there is no segregation in meiosis and mitosis ii Consequences 1 Gene produces will not be balanced anymore 2 Pseudodomiance allows recessive alleles on undeleted chromosome to be expressed 3 Haploinsufficiency some genes have to be present in two copies to produce enough gene product d Inversions troubles chromosomal rearrangements because the gene order is changed and can cause the gene to break into two pieces i Types 1 Paracentric inversions do NOT include the centromere 2 Pericentric inversions do include centromere ii Consequences eg position effect 1 Can cause inversion loop that would be present in meiosis e Translocations movement not crossing over between nonhomologous chromosomes i Types 1 Nonreciprocal translocation movement one way from one chromosome to another without equal change 2 Reciprocal translation the equal exchange of chromosomes of two nonhomologous chromosomes 3 Example Robertsonian translocation translation deletion causes some forms of Down syndrome ii Consequences 1 Altered gene expression due to position effect 2 Break may occur in a gene f Aneuploidy the number of chromosomes is altered addition deletion i How 1 Loss of chromosomes which has lost its centromere 2 Robertsonian translocation 3 Nondisjunction a 75 of human aneuploidies result from nondisjunction in mother ii Types 1 Nullisomy loss of both members of homologous pairs 2 Monosomy loss ofa single chromosomes a Example Turner syndrome 3 Trisomy gain of a single chromosome 4 Tetrasomy gain of two same homologous chromosomes iii Examples 1 Sex chromosome aneuploidies best tolerated aneuploidy XYY has very little impact due to lack of genetic info on the Y a Another example is Turners X and Klinefelter XXY 2 Autosomal aneuploidy smaller chromosomes more tolerated Down syndrome 21 UPD Uniparental disomy i Occurs when both chromosomes are inherited from one parent ii Can result from trisomy that is resolved by loss of a chromosome during embryogenesis Sex chromosome syndromes are more common that autosomal syndromes i Sex chromosomes syndromes Turner s Kleinfelters Poly X poly Y s ii Autosomal 21 1318 are survivable 1 All others are lethal unless individuals are mosaic Mosaicism an organism can have normal tissues and tissues that have chromosome abnormalities that result from nondisjunction Polyploidy one or more complete sets of chromosomes are added i How 1 Errors in meiosis 2 Events at fertilization a Dispermy a mechanism that is simultaneous fertilization of egg with two sperm i This is lethal most die before birth 3 Errors in mitosis following fertilization ii Types 1 Autopolyploidy all chromosome set are from same species 2 Allopolyploidy chromosome set are from different species a Results of hybridization followed by chromosomes doubling b Example modern wheat resulted from allopolyploidy iii Consequences 1 Problems with meiosis usually results in sterility a In agriculture the fruit that is sterile is seedless and larger k Fragile chromosomes most common form of inherited mental impairments Results from increase in number of trinucleotide repeats l Fragile sits prone to breaking i Trinucleotide repeat expansion lead to methylation and blockage of transcription fragility is related to length of repeat region ii Anticipation Genetic anticipation number of repeats increase in future generations causing symptoms to be worse m Rearrangements in Evolution importance i Example chromosome 4 different in humans and chimps by inversion Pericentric inversion does include centromere 1 The only major structural differences a Number of peri and Paracentric inversions b The recent fusion of two chromosomes to form human chromosome 2 c A reciprocal translation between gorilla chromsoems which correspond to human chromosomes 5 and 17 90100 identity at sequence level n Family members the coding DNA 0 Spacer DNA noncoding DNA between gene family members Table 93 Different types of chromosome mutations Chromosome Mutation Definition Chromosome rearrangement Change in chromosome structure Chromosome duplication Duplication of a chromosome segment Chromosome Deletion of a chromosome segment Inversion Chromosome segment inverted I80 degrees Paracentric inversion Inversion that does not include the centromere in the inverted region Pericentric inversion Inversion that includes the centromere in the inverted region Translocation Movement of a chromosome segment to a nonhomologous chromosome or region of the same chromosome Nonreciprocal translocation Movement of a chromosome segment to a nonhomologous chromosome or region of the same chromosome without reciprocal exchange Reciprocal translocation Exchange between segments of nonhomologous chromosomes or regions of the same chromosome Aneuploidy Change in number of individual chromosomes Nullisomy Loss of both members of a homologous pair Monosomy Loss of one member of a homologous pair Trisomy Gain of one chromosome resulting in three homologous chromosomes Tetrasomy Gain of two homologous chromosomes resulting in four homologous chromosomes Polyploidy Addition of entire chromosome sets Autopolyploidy Polyploidy in which extra chromosome sets are derived from the same species Allopolyploidy Polyploidy in which extra chromosome sets are derived from two or more species IV Ch 7 a Linked genes those that are close together on same chromosome travel together during meiosis do not usually sort independently b Morgan and Sturtevant i Morgan figured out the sex linkage with his y lab and with the help of Bridges ii Sturtevant another student of Morgan generated first map of chromosome based on recombination frequency c Recombinant vs Nonrecombinant i Recombination the switching of genes from one homologous chromosomes to another during late prophase ii Nonrecombination no crossing over offspring is same as parent d Consequences of linkage in next generation i With linked genes and some crossing over nonrecombinant progeny are predominant majority Therefore over representation of parents Not a 1111 ratio of independent assortment e Steward used frequency of recombination to determine the physical distance separating two genes on a chromosome i High recombination genes far away ii Low recombination genes close together f Recombination frequency i of recombination proaeny total of progeny X 100 ii Interchromosomal recombination between genes on different chromosomes arises from independent assortment in Anaphase 1 iii Intrachromosomal recombination between genes on same chromosome crossing over in prophase 1 g Cis vs trans i Cis coupling one chromosome has wild type alleles And the other chromosome has mutant alleles ii Trans repulsionquot each chromosome has one wild type and one mutant h Genes may be 1 On different chromosomes independent assortment occurs 2 Completely linked on same chromosome Being close together so crossing over is rare 3 Incomplete linkage genes on same chromosome but some distance apart allows some recombination i Determining gene distances i Add up all recombinant progeny divide by total number of progeny X 100 ii You can determine if it is a recombinant progeny if you compare it to the parents and it s different anywhere j Genetic maps use recombination frequencies to make chromosome maps i Distances are in terms of Map units centimorgans cM ii Limits 1 Recombination frequency cannot be greater than 50 for two genes because it would be impossible to discern between two genes that are far apart on the same chromosome and those on different chromosomes 2 Genes that are far apart can undergo double crossovers to make it seem like crossovers never occurred k Linkage groups distant markers can be tied together by intermediate markers i Intermediate markers allow a linkage group to span greater than 50 cM distance l Testcrosses i Two point test crosses test cross between two genes 1 3point crosses are more efficient than 2 point crosses because a Order of genes can be established in a single cross b Double crossovers can be detected providing more info i Double crossovers yields recombinant chromosomes with altered middle gene c In a 3 point test cross first figure out the group that represents the parental largest group i But in 2 point it would be the smallest group ii And in a single cross over it would fall in the middle m Interference once one crossing over occurs the chromosome now avoids adding any more crossing over near that interferes i The interference and Coefficient of coincidence COC of observed double crossovers of expected double crossovers Interference 1 COC If interference 1 no cross over events If interference 0 observed the expected the number of double crossovers 11 Molecular markers i ii They are like road signsquot and mile markersquot Types 1 RFLP Restriction fragment length polymorphism changes in DNA sequences that modify restriction enzyme recognition sites 2 VNTR Variable number of tandem repeats differences in copy number a Examples SSLP minisatellite microsatellites i Microsatellite markers di tri tetra nucleotide repeats CA CA CA CA CTG CTG CTG GAAA GAAA GAAA 3 SNP single nucleotide polymorphism single base change
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