Genetics Lecture Notes Week 3
Genetics Lecture Notes Week 3 85033 - GEN 3000 - 002
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85033 - GEN 3000 - 002
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This page Class Notes was uploaded by Toni Franken on Sunday January 24, 2016. The Class Notes belongs to 85033 - GEN 3000 - 002 at Clemson University taught by Kate Leanne Willingha Tsai in Summer 2015. Since its upload, it has received 54 views. For similar materials see Fundamental Genetics in Biomedical Sciences at Clemson University.
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Date Created: 01/24/16
GEN 3000 Notes Set 6 01202016 Dr Tsai Clemson University Chapter 3 Continued Beginning of Chapter 4 Chapter 3 Cont Pedigrees Pedigree charts can be used to decide whether or not the trait we re looking at is being inherited in a recessive fashion or a dominant fashion We ll start by looking at autosomal chromosomes in other words no sex chromosome involvement 0 Genetic diseases within the human population particularly recessive traits or diseases are relatively rare Recessive DiseasesTraits O Recessive traits or diseases A disease for which an individual must have two copies of the recessive allele in order to display the phenotype A recessive disease often skips generations If there is an affected offspring both parents HAVE to be carriers or also affected by the disease 0 Recessive diseases tend to be rare within a family If there is a huge generational skip but then a generation displays a great deal of a recessive disease there is most likely some level of consanguinity mating between related individuals If it is rare in the population but a family is consanguineous in any form you re more likely to see recessive alleles Autosomal Recessive disorders are more commonly seen in animal type pedigrees due to the higher instances of consanguinity Dominant DiseaseTrait 0 Genetic diseases can also be caused by dominant alleles so you only need one copy of the allele to get an affected offspring Every generation is going to have an affected individual If there is an unaffected individual born in a family line meaning they have two recessive alleles they will NOT be able to pass on the trait unless someone new brings it into the genetic line Generally affected individuals for a dominant disease or trait are going to heterozygous Hh instead of homozygous for the allele due to higher ratios of heterozygous genotypes 0 Example Waardenburg syndrome is an autosomal dominant trait that causes deafness fair skin white forelock and visual problems Note Not everyone draws their pedigrees in that standard format especially in animals like canines that are bred to many different individuals 0 Designed pedigree Within a designed pedigree you can often see a lot of backcrossing used lines down with gaps to show how they follow each other However any questions asked in this class will follow standard generation and numbering format Deciphering genotypes in pedigrees 0 Example A male individual with a family history of a recessive disease but who is not affected himself is to have an offspring with a female individual They want to know what the likelihood of their offspring having the disease will be 0 The disease is autosomal recessive meaning two recessive alleles must be present in order to be expressed Since the male is unaffected he either has Dd dD or DD and no possible chance of being a dd therefore we can eliminate this from possibility Therefore dad has a 23 chance of carrying the affected gene Mom s history is very important in this case She is unaffected so if there is no history of the disease in her lineage we can assume that she has a DD genotype and the offspring will have no chance of being affected due to the impossibility of a dd phenotype I However if mom m have a family history of the trait we must go back through her lineage to determine the likelihood of her being a carrier So let s say her parents are unaffected but she does have a sibling that is affected This means both of her parents carry the 1 gene meaning she has a 23 chance just like dad of being a carrier If the couple has a child and they are both carriers that offspring will have a IA chance of getting two d alleles All three of these probabilities would have to happen meaning we must take 23 x 23 X M 436 19 chance of the child being affected Chapter 4 Modification of Mendelian Ratios Vocab O O Allele Different forms of the same gene If the allele loses its ability to work properly it has a lossoffunction mutation Lossoffunction mutation A partial loss of function black pigmentation loses some capability to create a grey color or loses color partially Null allele Allele is not working at all black pigmentation no longer causes black coloration Gainoffunction mutation The allele is working so much that it ends up gaining more work for the protein or doing it at the wrong time black pigmentation is showing up in the wrong spot or is just a very dark color Change of functionneutral mutation alleles can change function as well This is a neutral mutation that doesn t affect what happens but it does something else Gene Interaction Some genes interact together to create different possibilities Phenotypes vary XlinkageYlinkage Sexchromosome linkage 0 Other allele notation So far when differentiating alleles we ve been using capital and lowercase However this nomenclature isn t always applicable or preferred 0 Wild Type or Mutant Allele The wildtype allele is considered the most common allele appearance in a population Anything that alters the wildtype is mutant Red eyes in the fruit y are considered a wildtype allele So instead of denoting an allele as dominant or recessive we consider it or where is the wild type and the is for the mutant 0 Superscripts You can also distinguish between different alleles with numbers or letters as superscripts allele 1 and 2 for example R1 or R2 two forms of the allele Incomplete Dominance A blending of dominant and recessive characteristics to create a new phenotype When Mendel set up his experiments the offspring of two parents looked exactly like one parent or the other However it doesn t always work that way 0 If we had homozygous of each parent of a certain colored plant and the crossed PP x pp all Pp the offspring would have characteristics of both parents creating an intermediate color Then in the second generation Pp x Pp lPP2Pp1pp you get three different genotypes and three different phenotypes In the case of eggplants the parent generation would be a dark purple crossed with a white plant the F1 generation would be all lighter purple violet plants and the F2 generation would have a 121 ratio of the three colors Codominance Different than incomplete dominance Instead of a blend you clearly see the effect of both alleles at once The example of that is a blood antigen group There are two different alleles LM and LN Homozygous LMLM LNLN are only going to produce one antigen while a heterozygous allele combo LMLN produces BOTH M and N antigens Sickle Cell Anemia Can be classified differently depending on how you look at it Individuals that are heterozygous will have some of both cell shapes wildtype round mutant sickle You can distinguish between the alleles in a blood sample and could consider this a codominance due to the visible effect of both alleles But if you look at the individual patient not just their blood they must be homozygous recessive to actually be considered to have Sickle Cell Anemia Heterozygous generally have no phenotypic effect on the health of the individual GEN 3000 Notes Set 7 01232016 Dr Tsai Clemson University Chapter 4 Continued from video lecture Modi cation of Mendelian Ratios 0 Recessive Lethality O Cuenot In 1900s Cuenot was attempting to replicate and build off of the work of Mendel He began to do crosses in mice for color traits 0 He set up his experiment the same way that Mendel did and found that there was the expected 31 ratio between gray and white mice Then when he tried a different phenotype Yellow crossed with gray he originally believed he was again getting the 31 ratio in F1 of the cross As he continued to do more generations he found that he was getting no truebreeding yellow mice YY and was getting a 21 ratio of yellow to gray instead of 31 0 It turns out that this yellow allele in mice is a pleiotropic gene a gene that can impact several aspects of the overall phenotype When looking at the phenotype the Yellow gene does appear dominant However if two copies of Y were present the mice were still born Therefore the homozygous dominant gene is recessively lethal 23 of live progeny are Yy yellow 13 of progeny are yy nonyellow 39 Note even though lethality is related to a dominant gene the lethality itself is recessive because it is hidden in heterozygous mice Yy 0 Another example of recessive lethality The manx phenotype in cats includes the ML allele the lethal allele that stops the spine from developing properly The M allele is the normal one If only one copy of the ML gene is in the animal it is nonlethal and only the tail is missing However if two copies of the ML are present it is embryonic lethal making it recessively lethal for the dominant allele 0 Dominant Lethality 0 There are also examples of dominant lethal alleles which can only happen and surivive in a population if lethality is late onset after reproductive capabilities An example of this is Huntington s disease in humans It only takes one copy of the dominant allele to cause lethality 0 Multiple Alleles Genes can have more than just two alleles Within any giving individual there will be two alleles but within the total population there can be numerous alleles 0 Example The ABO blood group has three alleles the A allele IA for the A antigen the B allele IB for the B antigen and the 0 allele i that simply makes no antigen The 0 allele i is recessive to both IA and IB while IA and IB are Codominant This results in various combination possibilities 0 blood type has to be ii and AB blood type has to be IAIB However when only one antigen is expressed the genotype may be IAi IAIA IBi or IBIB 0 ii is the 0 universal donor due to lacking antigens AB IAIB is the universal recipient because it is used to both antigens but can also receive the 0 type that lacks antigens Some genes have a great many allele possibilities In the Drosophila the fruit y there are at least 100 allele combinations for the eye color They are all designated with w where n is the allele designation Probability Within a single individual we will still only have two alleles However our possible genotypes and phenotypes are going to change We can still use probability we just have to modify it Example Cross two parents and look for possible blood types and chances of albinism aa or pigmentation A of skin Cross is between two pigmented parents one with type A blood and one with type B AalBi X AalAi lt 34 A pigmented 14 aa blood AaIBi x AaIAi Gene Interactions 14 IAIB AB blood type of pigmented with type AB 14 lAi A of pigmented blood type with type A 14 lBi B blood type 14 ii 0 blood type 14 IAIB AB blood type 14 lAi A blood type 14 IBi B blood type 14 ii 0 blood type of pigmented with type B of pigmented with type 0 116 chance of albino with type AB blood 116 chance of albino with type A blood 116 chance of albino with type B blood 116 chance of albino with type 0 blood 0 More than one gene contributes to the same phenotype Both genes work together to create an overall appearance 0 For example In peppers there are two alleles that contribute to coloration Rr and Cc R is dominant and produces a red color An r is recessive and produces no color C is dominant and breaks down chlorophyll to get rid of the green color while the c is the recessive allele that allows the chlorophyll to remain intact producing the green color So if the RRCC red pepper is crossed to an rrcc green the F1 generation appears to be simple recessive However in the F2 generation four phenotypes make an appearance You get 916 Red pigments RC 316 of a brownish color Rcc 316 yellow peppers rrC and 116 green rrcc 0 Recessive Epistasis Sometimes one gene can completely hide what s going on at another gene if two recessive alleles are present 0 Labrador retriever coloration Labs can be black chocolate or yellow The first gene B or b is the actual pigmentation of Black B or brown b where B is dominant to b The second gene is responsible for attaching pigmentation to hair color but is only functional at dominant E and nonfunctional at recessive e 0 Black genotypes are BBEE BbEE BBEe or BbEe Chocolate are bbEE or bbEe and Yellow are BBee Bbee bbee As long as there is an E present the pigment will be attached to the hair If it is homozygous for e ee then the allele is non functional and produces a yellow color This is our epistatic gene which will mask the effect of the hypostatic or hidden gene In this case it is the Bb gene 0 How does this affect our ratios We start with a black lab and yellow lab true bred both BBEE X bbee I The F1 generation will produce all black puppies BbEe I F2 generation BbEe x BbEe will give us a 934 ratio of blackbrownyellow We can break it down since we know every yellow lab has to be ee every black lab has BE and every chocolate lab has bbE I As a side note you can distinguish between a BBeeBbee and bbee the BBeeBbee will be yellow with a black nose and the bbee will be yellow with a brown nose giving us the 9331 ratio 0 Bombay Phenotype I Recessive epistasis example in humans A woman s blood showed no antigens so they gave her some 0 blood and she had a reaction The doctors couldn t figure out why and found that she has a parent that was AB meaning they would HAVE to pass on an A or B allele making the woman unable to be type 0 Her children also exhibit the B allele while her husband has no B allele only A and 0 It turns out that she has a mutation in the h antigen which is responsible for the addition of the A and B antigens to the blood cells She had the B allele but the B antigens could not attach to her red blood cells making her appear to be an 0 blood type Hh individuals type as 0 but cannot receive 0 blood This is recessive epistasis 0 Dominant Epistasis Where one gene can completely hide what is going on at another loci with the presence of only 1 dominant allele 0 Example A certain type of squash can be one of three colors White Green or Yellow This requires a process where compound A in a white squash is converted by Enzyme I to compound B to create a green squash Then compound B is converted by Enzyme II to create compound C resulting in a yellow squash If this pathway gets interrupted the color expectation changes I The ww genotype allows the first step to occur properly converting to compound B If there is a W present it inhibits it to change resulting in a White squash If compound B is allowed to continue but the enzyme 11 has yy it inhibits enzyme 11 from changing compound B to compound C keeping the squash green If there is at least 1 Y allele the enzyme is allowed to continue If the squash is WY or Wyy the squash is white since the W stops the process right at the beginning The W gene is epistatic to the y gene Yy is the hypostatic gene If the squash is wa the squash is yellow If the squash is wwyy the squash will be green 1231 ratio of white greenyellow 0 Complementation Determining if mutations are in the same or different loci 0 Example Harebell plants usually produce blue owers the wild type gene wt Mutant plants produce white owers of which the white gene A B or C is recessive to wt I For every of these plants we will set up Mendelian crosses Two pure white mutants crossed AAwtwt X wtwtBB thBwt which produces blue owers because we have a wt allele for each gene A and B complement each other when bred because their mutations are one different genes I If the mutations were in the same gene AAwtwt X BBwtwt when the cross is carried out we ll end up with ABwtwt Since we have two mutant copies on the first gene we do not see complementation We have a homozygous mutant even though they are two different mutations We CANNOT get a wild type from this cross 0 Penetrance and Expressivity o Incomplete Penetrance Genotype does not always produce the expected phenotype Example an individual that is heterozygous for polydactyly having extra fingers or toes has the GENOTYPE to be polydactyl but may not be phenotypically polydactyl We can calculate the number of people that typically shows the phenotype to get the level of penetrance 0 Penetrance Percentage of individuals having a particular genotype that express the expected phenotype if 45 out of 50 people exhibit trait Penetrance 4550 9 90 Variable Penetrance will result in some individuals showing the trait completely and others not showing it at all 0 Expressivity Degree to which a character is expressed small nonfunctional digit versus a fully functional additional digit Variable Expressivity will show all individuals showing a trait but to varying degrees 0 Variable Expressivity and Penetrance In a group of individuals with the exact same genotype some will express a trait to varying degrees but others will not be affected at all 0 Temperature Effect Some alleles phenotype is determined by temperature 0 Himalayan rabbits They contain a temperature sensitive allele that makes a black pigment the proteins of which are sensitive to heat If the rabbit grows up in a warm environment above 30 C the pigment will not show up giving a completely white animal If they grow up in a cooler environment 20 C or less they will have black extremities At 25 C some pigment may show up making it gray 0 Norm of Reaction Range of phenotypes produced by a genotype in different environments If you were to apply an ice pack to the body of the rabbit the hair could grow back into a dark pigmented spot 0 Sex chromosomes 0 Sexlinked characteristics Involves genes located directly on the sex chromosome Humans and Fruit Flies XX female XY male In the next generation you would expect a 5050 split of male and female offspring The female gives an X to every child The male gives half of his offspring an X and half of his offspring a Y Thomas Hunt Morgan Worked mostly with fruit ies through which he first explained sexlinked inheritance because he discovered that a single male in his fruit y colony had white eyes so he set up crosses He assumes that W red is dominant over w white WW female x wwmale would give all Ww redeyed offspring Then in the next generation Ww x Ww get 31 ratio red to white eyes However he found that all of the whiteeyed ies were males There were NO females with white eyes So Morgan did a reciprocal cross of a Whiteeyed female with a redeyed male which produced IA redeyed males IA redeyed females 14 whiteeyed males and IA redeyed females He concluded that this trait is not independent of sex The males only received 1 copy of the X so they must ve gotten it from mom Hemizygosity Have one copy of a gene in a diploid cell Males cannot be homozygous or heterozygous for the gene located on the X chromosome 0 Xlinked recessive RedGreen color blindness is one of the most common sexlinked traits in humans It is called Xlinked color blindness If a normalcolor vision female XJ39X has children with a colorblind male X Y the female can ONLY pass on the wild type allele The male will pass on the color blind allele to all daughters and the Y to all of his sons All children will have normal Vision due to normal alleles of mom In the reciprocal cross a colorblind female XquotXc with a normalcolorvision male XY their daughters will all be normal colored vision due to one color blind allele from mom and one normal from dad All sons however will be color blind due to the X only from the colorblind female Males therefore are more commonly affected than females due to them having only 1 X chromosome Affected males CANNOT pass the trait to their sons since they contribute the Y chromosome I Another example of an Xlinked recessive disease is hemophilia A a disease of the royal family It is believed that Queen Victoria was the first carrier 0 Xlinked Dominant Traits I Do not skip generations and affected males pass to all daughters and no sons Heterozygote females pass the trait to half of their sons and half of their daughters Looking at an affected father can be most telling when looking at sexlinked traits An example of this is hypophosphatemia Familial vitamin Dresistant rickets 0 Ylinked traits Will ONLY appear in males in every generation because only males carry a Y 0 Sex in uencedlimited Genes on autosomal nonsex chromosomes that are more readily expressed in one sex 0 Sex in uenced I Example If a beardless male goat BB is crossed with a bearded female BbBb to get BBb the male offspring will be bearded and the female will not In other words the Bquot gene is recessive in females and dominant in males Males will express a beard in homozygous and heterozygous for Bb genes Only homozygous Bb females will have a beard I Human Example Male Pattern Baldness Pattern baldness is autosomal and can be inherited from either parent but it is in uenced by the sex of the individual If men just get one bald allele they will show the balding phenotype whereas females require two Castration limits baldness so testosterone seems to have an effect even though it isn t a likely practice 0 Sex limited These traits look like sexin uenced characteristics but will completely limited to one sex or the other ZERO penetrance in one sex Cock feathering is autosomal recessive HH males are hen feathered as are HH females Hh males and females are both hen feathered Males with hh will be cock feathered while hh females are still hen feathered 0 Genomic Imprinting Genes whose expression is affected by the sex of the transmitting parent 0 There are two copies of each of these genes However with each new generation the genes are marked to show that they came either from mom or dad The body does not want both to be working or else they will produce too much product so it will turn off one from mom or one from dad This was discovered by removing one chromosome from the gametes of mice If only one chromosome was present from the egg and both from the sperm there would be normal placental development but abnormal embryo structures If there was only one sperm chromosome but both from mom there will be an abnormal placenta and normal embryo structures This means that both genes must contribute to an extent It is believed that this happens by methylation of DNA epigenetic modifications It does not affect all genes Epigenetics Genome modifications that cause functional differences but do not change the nucleotide sequence 0 In the human the PraderWilli syndromeAngelman syndrome are classic examples of genomic imprinting I PWS Small hands feet short stature mental retardation frequently become obese due to increased appetite inherited from the father and is caused by the absence of segment 1113 on the long arm of the paternally derived chromosome 15 But if no deletion is detected both copies of 15 came from mom called uniparental disomy Two copies of the same chromosome from one parent I Angelman Syndrome Constant laughter puppetlike uncontrolled movements due to same deletion in chromosome 15 1113 but from mom s chromosome or if both copies came from the father For normal development the offspring needs one copy from each parent One copy from each is turned off 0 Cytoplasmic Inheritance Cytoplasmic genes which are usually inherited entirely from only one parent usually comes from the female due to sperm mitochondria not adding into the zygote O Mitochondria They contain a small amount of genetic information and replicate on their own outside of the nuclear system When cell division occurs there s no mechanism to divide the types of mitochondria equally giving a random distribution Heteroplasmy is the presence of multiple copies of mitochondrial genomes This makes it hard for us to identify mitochondrial diseases If all mitochondria are heavily mutated it is lethal to the cell Slight mutation can allow survival We see mitochondrial diseases passed from the mother to the offspring If all or almost all mitochondria are mutated the female will pass it on to all offspring but a male will not pass it on O Chloroplasts The fouroclock plant comes in a variegated form where the chloroplasts are mutated and nonfunctioning making a portion of or the entire plant white If a plant ends up completely white it is lethal because the plant needs functioning chloroplasts to survive Therefore parent plants MUST be partially green The female pollen from a White branch will produce all White offspring All green mother pollen produces green offspring Variegated offspring will create a mix of white green and variegated offspring 0 Maternal effect Nuclear genotype of the maternal parent determines phenotype in next generation 0 Example Snails have shells that can coil in both directions where dextral right coiling is dominant Wild type ss and sinistral left coiling is recessive ss If a dextral homozygous male ss is crossed With a homozygous sinistral ss female the entire F1 generation will end up sinistral despite the genotype suggesting it is dextral This is because mom s genotype was sinstral In this generation it appears the male doesn t have an impact on shell coil Snails can crossbreed or selffertilize If the F1 generation selffertilized so ss X ss you get all dextral shells IA ss 12ss and 1Ass because the maternal genotype says dextral This F2 generation shows that the male genetic contribution is important
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