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Use Definition II

Trigonometry | 7th Edition | ISBN: 9781111826857 | Authors: Charles P. McKeague ISBN: 9781111826857 186

Solution for problem Problem 2 Chapter 2.1

Trigonometry | 7th Edition

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Trigonometry | 7th Edition | ISBN: 9781111826857 | Authors: Charles P. McKeague

Trigonometry | 7th Edition

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Problem Problem 2

Use Definition II

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Chapter 23: - Functional genomics: Aims to figure out the roles of genetic sequences in species o Aims to understand gene function o Proteome: Entire collection of proteins that an organism can make o Proteomics: Work towards understanding functional roles of proteins in species § Aims to understand the interplay among proteins o Bioinformatics: Uses computational/mathematical approach to analyze biological information § Often thought of in terms of extracting information from genetic data - Microarray can identify genes that are transcribed o Can analyze 1000s of genes at a time o DNA microarray is a small silica or glass slide that is dotted with many sequences of DNA § Each sequence is complementary to known gene § Fragments are made synthetically § These sequences of DNA will act as probes to identify genes that have been transcribed o Steps § First isolate mRNA from cell § add reverse transcriptase with fluorescently labeled dNTPs § Overlay microarray with fluorescent cDNAs § Wash off excess cDNAs that haven’t yet bound § Placed in laser scanner to see fluorescent spots § Are used to analyze gene regulation and expression - Chromatin Immunoprecipitation (ChIP): determines if proteins can bind to specific regions of DNA in chromatin of living cells o Proteins in living cells are crosslinked to DNA with formaldehyde (in cell) o Cells are lysed and DNA is broken into small pieces o Antibody is used to precipitate the protein of interest o DNA is chemically freed from the cross-links o DNA amplified via PCR o Sequenced of DNA is identified directly or by using it as a probe on a microarray § Fluorescent spots on microarray tell us where in the genome the protein binds - Gene knockout collections o Goal is to determine function of every gene in a species genome o Can get large number of one organism and just knockout one gene in each § The phenotype could indicate function § Could combine knockouts to study pathways o Can knockout via transposable elements and homologous recombination o Can’t determine protein function if the knockout is lethal - Bioinformatics o Using a computer to analyze genetic sequences o 3 components § Computer § Computer program • Defined series of operations that can analyze data in desired manner § Data o First step is generating a computer data file (suitable for analysis) § Collection of information in a form suitable for storage and manipulation by a computer o For program aimed at translating § DNA sequence input § Tell computer to translate § Computer reads all three reading frames (actually six, 3 forward and 3 back) and outputs whichever one the reader wants • Wrong reading frames are short because they experience a stop codon prematurely • Longest reading frame is usually the correct one o Much faster than a human can work and completely accurate o Useful when user does not know where start codon is § Or which direction the coding sequence goes o Amount of genetic information stored in research databases is enormous § Large numbers of computer data files are collected and stored in a single location, a database • Files are typically annotated with gene sequence, name of gene, description of gene and significance of gene o Different computational Strategies § Computer programs can be designed to locate to locate meaningful features within very long sequences § Imagine 54 random English letters • One program could locate all the English words within the sequence • Another could locate a series of words that make up a grammatically logical sentence • Another can locate patterns of letters that occur in both the forward and reverse directions § Sequence Recognition: Program has information that specific sequence of symbols has special meaning • First program (info = dictionary to make words) • Second program (sequence organization) § Pattern recognition: Does not rely on specialized sequence information rd • Look for patterns of symbols (3 program) o Identification of structural genes § Locate specialized sequences (sequence elements) within a very long sequence • Search by signal: program looks for known sequence elements that are normally found in genes o Promoter, start/stop codons • Search by content o Identifies sequences that differ significantly from a random distribution o Codon bias § Locate an organization of sequences or sequence elements • 2 program § Locate a pattern of sequences • 3 program § Can locate coding regions by searching for translational reading frame • ORF (open reading frame) is a nucleotide sequence that does not contain any stop codons • In prokaryotes, long ORFs typically means gene sequences • Doesn’t work as well in eukaryotes to find ORFs because of the presence of introns • Computer program can translate genomic DNA sequences into all three frames and look for the longest ORF o It is also possible that a reading frame could proceed from right to left o Programs can identify homologous sequences § DNA sequencing allows geneticists to examine evolutionary relationships at molecular level § Homologous means derived from same ancestral gene • Very similar sequences!!!! • Have accumulated some mutations over time that have made them slightly different § When two homologous genes are found in different species they are orthologs § Paralogs: two or more copies of homologous gene within the same organism • A gene family consists of two or more copies of homologous genes within the genome of a single organism § Homologous does not mean similar • Homology implies a common ancestry • Similarity means sequence similarity • In many cases, similarity is due to homology, but this is not always the case § Homology is useful because it helps determine the function of proteins in other organisms • Homology between genetic sequences can be identified by computer programs and databases • BLAST (basic local alignment search tool) compares your sequence to other sequences in organisms o Starts with genetic sequence and locates homologous sequences in large database § Homology in protein sequence is easier to find than DNA sequence homology o Can show how similar a protein is in different organisms § Can then determine function of proteins easily o Blast search output is based on E-value § Represents likelihood match is due to random chance § Small E-value means it is unlikely similarity is due to random events (genes are likely homologous) o The order of matches follows the evolutionary relatedness of the various species Chapter 24: - Thousands of genes cause diseases in humans o Many occur due to mutations in a single gene § Also can be caused be mutations in multiple genes • Multifactorial - Observations of human diseases o Geneticists want to know the relative contributions from genetics and environment o Geneticists cannot conduct crosses o Must rely on analyses of families that already exist through pedigrees - Rules (Many genetic diseases correlate with multiple of these): o When individual exhibits disease, it is more likely to occur in blood relatives than general population o Identical twins share same disease more often than fraternal twins § Identical twins are also called monozygotic twins (formed from the same sperm and egg) § Fraternal twins are also called dizygotic twins (formed from separate pairs of sperm and egg) § Concordance: Degree to which a disease is inherited • Refers to percentage of twin pairs in which both twins would show the disorder/trait • Theoretical value is higher than actual value o Genetic disease does not spread to individuals sharing similar environmental conditions o Different populations have different frequencies of disease o Disease develops at characteristic age § Age of onset o Human disease may resemble a genetic disorder that is already known to have a genetic basis in an animal o Correlation is shown between a disease and a mutant human gene or a chromosomal alteration - Pedigree analysis: Pattern of inheritance of monogenic disorders can be deduced by looking at pedigrees o Must obtain data from large pedigrees with many affected individuals - Tay-sachs disease: individuals appear healthy at birth but develop neurodegenerative symptoms at 4-6 months (AOO) o Symptoms = cerebral degeneration, blindness and loss of motor function o Die at 3 or 4 years of age o More frequent in Jews o Is the result of a mutation in a gene that encodes the enzyme hexosaminidase A (hexA) § Breaks down lipids § If hexA is not active, accumulation of lipids occurs in the cells of the CNS, which causes the neurodegenerative symptoms o Inherited in an autosomal recessive manner § Four features of autosomal recessive inheritance • Affected offspring can have 2 unaffected parents • When two unaffected heterozygotes have children, 25% will be affected on average • Two affected individuals will have 100% affected offspring • Occurs in same frequency in both sexes § Disorders that involve defective enzymes/proteins typically have autosomal recessive inheritance mode of transmission • Heterozygote carrier has 50% of the normal enzyme o This is sufficient for a normal phenotype • Common way of inheritance - Huntingtons Disease: Degeneration of neurons in the brain o Personality changes, dementia, and early death o Is the result of a mutation in a gene that encodes a protein termed huntingtin § Causes an aggregation of protein in neurons o Autosomal dominant inheritance o Five common features: § Every affected individual has at least one affected parent • Can be altered by reduced penetrance § Affected individual with 1 affected parents will produce 50% affected offspring § 2 affected heterozygotes à 25% unaffected offspring • 75% affected § occurs with the same frequency in both sexes § Homozygote is more severely affected (often is lethal) compared to the heterozygote § Common explanations for dominant disorders: • Haploinsufficiency: o heterozygote has 50% of normal protein o this is not enough for the normal phenotype • Gain of function mutations: o Mutation changes protein so it gains a new function • Dominant-negative mutation: o Change of gene product acts antagonistically to the normal product § Autosomal dominant diseases are not as common as autosomal recessive, but are not rare - X-linked recessive inheritance o Problem more so for males § Only have one copy of the x chromosome (hemizygous) o Female heterozygote will pass trait to half her sons o 3 common features of X-linked recessive inheritance: § Males are more likely to exhibit the trait § Mothers of affected males often have brothers/fathers who are affected with the same trait § Daughters of affected males will produce 50% affected sons - X-linked dominant inheritance is rare o Characteristics of such disorders: § Males are often more severely affected • Females may be less affected due to wild-type copy on second X § Females are more likely to exhibit the trait when it is lethal to males § Affected females have a 50% chance of passing the trait to daughters o Often caused by a new mutation - Genetic disorders often exhibit locus heterogeneity o Locus heterogeneity: refers to the phenomenon that a disease can be caused by mutations in two or more different genes - Cancer: caused by mutation in somatic cells, not usually inherited (may have genetic predisposition) o Caused by uncontrolled cell division o Genetic disease at the cellular level o More than 100 kinds are known § Usually grouped by cell type it originates in o Characteristics: § Originate in single cell • Clonal § At the cellular and genetic levels, it is usually a multistep process • Begins with precancerous genetic change (benign growth) • Additional genetic changes cause progressive cancerous cell growth § Once cell becomes malignant, the cells are invasive and causes problems • Can travel through bloodstream to the rest of body à metastatic o Cancer can be caused by viruses § Not very common § Transformation: process of converting a normal cell into a malignant cell § Typically, cancer-causing viruses are not very potent at inducing cancer because they are inefficient at transforming o Oncogenes: Promote abnormal cell growth § Gain of function mutation § Cell cycle is regulated by growth factors • Initiate cascade that causes cell division • Growth factors can mutate to become oncogenes • Mutation will cause cell to think growth factor is present when it isn’t § Proto-oncogenes: normal cellular genes that can mutate to become oncogene • Expression becomes abnormally active o Gain-of-function mutation • Three ways this can occur: o Oncogene can be overexpressed o Oncogene can produce aberrant protein that is overly active o Oncogene may be expressed in cell type where it is not normally expressed • Mutations can convert normal ras into oncogenic ras o Keep Ras in active state constantly (cell doesn’t stop dividing) o Can also decrease the GTPase activity o Or increase the rate of ADP/ATP exchange • Proto-oncogenes can be converted into oncogenes in in four ways o Missense mutations § convert ras genes into oncogene § Can be caused by carcinogens o Gene amplification o Chromosomal translocations § Cause expression in cells where it shouldn’t be § If you know enough about cancer, you can create drug to block that action o Viral integration § Can integrate into host DNA as part of their life cycle § Causes enhanced activation o Tumor suppressor genes: § Prevent proliferation of cancer cells • If inactivated (loss of function), cancer cells are not suppressed • TS gene can inhibit activator • First identification of a human tumor-suppressor gene involved studies of retinoblastoma o “two-hit” hypothesis: a heterozygote has one normal copy and one defective copy of rb gene and in the retina of the eye, the patient suffers a second hit that makes the normal copy defective, giving them retinoblastoma o when both copies of the Rb protein are defective, the E2F protein is always active, leading to uncontrolled cell division § P53 Gene: Master tumor suppressor • 50% of all human cancers are associated with defects in the p53 gene • Primary role of p53 is to determine if a cell has incurred DNA damage or not o If so, p53 will promote three types of cellular pathways to prevent the division of cells with damaged DNA § Activates genes that arrest cell division and generally repress other genes that are required for cell division § Activates genes that promote DNA repair § Activate genes that promote apoptosis • Programmed cell death § General Roles: • Can have direct effects on negative regulation of cell division • Can play role in maintenance of the genome § Loss means no surveillance on cell integrity (not cancer causing!) • P53 can no longer monitor mutations § Function of tumor-suppressor genes can be lost in three ways: • Mutation in tumor-suppressor gene itself o Promoter could be inactived o Early stop codon • DNA methylation o Methylation of CpG islands near the promoters of tumor-suppressor genes, which inhibits transcription • Aneuploidy o Chromosome loss can contribute to cancer progression if the chromosome carries at least one tumor suppressor gene § Most cancers involve multiple genetic changes • Can keep making changes after initial cancerous mutation, which leads to malignancy • Often is a progression of mutations (random order) that accumulate and make the cancer difficult to treat o Inherited forms of cancer § Often involve germ-line mutations (5-10% of all cancers) • Offspring have higher chance of developing cancer because of their inherited predisposition § Most inherited forms of cancer involve a defect in tumor suppressor genes § Predisposition is often result of being heterozygous for one of the genes § Cancer results from loss of normal copy • Known as loss of heterozygosity (LOH) • Inherited in dominant manner • Can result from a point mutation in the normal allele • Can also occur if chromosome carrying the good copy is lost - Personalized Medicine o Use of patients genotype to select treatment suited for patient o Can be used to choose the best treatment for cancer or to determine best drug dosage o Molecular profiling § Using various methods to understand molecular changes behind a disease § Allows: • Differentiation between cancers which might look similar under a microscope • Predicting which drugs target altered genes § DNA microarray can be used for molecular profiling § Hopefully allows researchers to find drug targets • Want to target over expressed genes o Pharmacogenetics § Drugs can have very different effects in humans dependent on: • Rate of transport from digestive track or into target cells • Ability to affect target protein • Ability to be metabolized by the liver • Rate of excretion of drug from body § Lots of variety among people

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Textbook: Trigonometry
Edition: 7
Author: Charles P. McKeague
ISBN: 9781111826857

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