Understanding Chi-Square Test & Genetic Linkage: Hypothesis Testing & Recombination, Study notes of Genetics

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GENE book notes CHAPTER 1 - genes – DNA regions that encode proteins - Chromosomes – DNA molecules carrying the genes - Genome – entire collection of chromosomes in each cell of an organism CHAPTER 2 - Genes – basic units of biological information o Region of DNA that encodes a specific protein or a particular type of RNA - Heredity – way genes transmit biochemical, anatomical, and behavioral traits from parents to offspring - Genetics – science of heredity - Themes from Mendel o Variation (alternative forms of a trait) is widespread in nature o Observable variation is needed for following genes o Variation is not by chance, but by genetic laws o Heredity laws apply equally to all sexually reproducing organisms - To study genetics you need: groups of organisms, good records = development of theoretical idea of origin - Artificial selection – purposeful control over mating by choice of parents for the next generation - Blended inheritance – idea that parental traits become mixed and forever changed in the offspring - Self-fertilization/selfing – both egg and pollen come from the same plant - Cross-fertilize - Reasons pea plants were good examples o Organisms had both male and female organs in the same flower o Each generation produced large numbers of individuals within a short growing season - Things Mendel did differently than people before him o He picked the pea plant o He examined the inheritance of clear-cut alternative forms of particular traits (no intermediate forms)  Discrete traits  Opposite of continuous traits o Collected and perpetuated lines of peas that bred true o Cross-bred pairs to make hybrids o Carefully controlled his matings o Worked with large numbers of plants, counted all offspring, used numerical analysis, and compared results with predictions from his models (quantitative approach) - Pure-breeding lines – matings produce offspring carrying specific parental traits that remain constant from generation to generation - Hybrids – offspring of genetically different parents - Reciprocal crosses – reversing traits of the male and female parents to control whether a particular trait was transmitted via the egg cell within the ovule or via a sperm cell within the pollen o Similar progeny in these tests disproves idea that one parent contributes more to the next generation, but they contribute equally to inheritance - Parental generation (P) - First filial (F1) – progeny of the P generation - Monohybrid crosses – using hybrids for a single trait o Allowing F1 to self-fertilize - Second filial (F2) – progeny of the F1 generation o Creates a ratio of 3:1 - Reappearance of the recessive trait disproves blending o If blending occurred, one of the traits would be absent from both the F1 and F2 generations - Genes – units of inheritance from parents - Alleles – alternative forms of a single gene o Ex – the gene for pea color has yellow and green alleles - Monohybrids – individuals having two different alleles for a single trait o Ex – Mendel’s hybrids of the F1 generation of pea plants had a dominant allele and a recessive allele - Recap of Mendel’s experiments/reasoning – Mendel started with two plants that were true breeding for the same trait, but had different phenotypes. For example yellow peas and green peas. This means that one was homozygous dominant and one was homozygous recessive. When the parents were bred, the F1 all had the same phenotype of the dominant phenotype, but they were heterozygous dominant. Mendel proved this with the F2 generation because the recessive trait that was absent in the F1 generation reappeared in the F2 generation in a 3:1 ratio. Some of the plants were again homozygous recessive and showed the trait that had been missing. The other plants were either homozygous dominant, or heterozygous and showed the dominant trait. - The law of segregation explains how genes are transmitted - Gametes – specialized cells that carry genes between generations o Eggs and sperm - Zygote – fertilized egg - Law of segregation – The two alleles for each trait separate (segregate) during gamete formation, and then unite at random, one from each parent, at fertilization - Segregation – equal segregation in which one allele, and only one allele, of each gene goes to each gamete - Product rule – the probability of two or more independent events occurring together is the product of the probabilities that each event will occur by itself - Sum rule – the probability of either of two such mutually exclusive events occurring is the sum of their individual probabilities - The segregation of dominant and recessive alleles during gamete formation and their random union at fertilization could explain 3:1 ratios from allowing hybrids to self- fertilize - Codominant – both traits of the parents show up equally in F1 hybrids o Each genotype has its own phenotype so ratio of F2 is 1:2:1  1 parent: 2 F1: 1 parent o ex – distinguishing molecules of red blood cells  IA and IB, that can be homozygous for one or heterozygous and have both, but determines what surface sugars a red blood cell with show o Molecular level phenotypes are often determined by codominant alleles - Summary of dominance stuff o Complete dominance – F1 progeny look like one of the true-breeding parents o Incomplete dominance – hybrids resemble neither parent and do not show either true breeding trait o Codominance – phenotypes of both pure-breeding lines are shown in the F1 hybrid o Dominance is determined by the phenotype of the F1 generation o F2 ratios  3:1 = complete dominance  1:2:1 = incomplete dominance or codominance - The phenotypic dominance results have nothing to do with the allele segregation - There can be more than two alleles for a gene o Ex – human blood types  3 alleles = IA, IB, and i  Type A = IAIA, IAi  Type B = IBIB, IBi  Type AB = IAIB  Type O = ii  Each person only gets two alleles so there are 6 possible genotypes - Alleles are not inherently recessive or dominant, but can only be classified when compared to other alleles - New alleles come from mutations - Mutations – chance alterations of the genetic material that arise spontaneously in nature o Make it possible to follow gene transmission - Alleles that give a survival/reproductive advantage to individuals so they can make more offspring are likely to increase in the population - Allele frequency – percentage of the total number of each allele out of the gene copies o Number of individuals x 2 = number of copies of a gene in a given population  Because each organism carries two copies of every gene - Wild-type allele – allele whose frequency is greater than 1% - Mutant allele – allele whose frequency is less than 1% o Ex – mouse fur has 14 mutant alleles that can change color - Monomorphic – a gene with only one wild-type allele o Ex – A in mice is the only wild-type allele for the agouti fur coat gene and has a frequency greater than 99% - Polymorphic – genes with more than one wild-type allele o Ex – ABO blood system – IA, IB, and i are all wild-type alleles - Pleiotropy – phenomenon of a single gene determining a number of distinct and seemingly unrelated characteristics - Lethal alleles o Ex – mouse light yellow coat color (Ay)  Yellow mice are heterozygous for the agouti gene and Ay (mutation)  Yellow has to be dominant to agouti, even though agouti was dominant to at and a mutations for black color  Yellow + yellow = 2 yellow:1 agouti  There is never a pure-breeding yellow because two Ay genes is lethal - Recessive lethal allele – an allele that negatively affects the survival of a homozygote o Ex – Ay in mouse fur color proves lethal if offspring receives two copies o Some may allow offspring to live past birth and die later because of genetic consequences  Ex – Tay-Sachs disease in humans o These alleles are usually not passed on because the affected person dies before having children  Stay in population because of heterozygotes o Late-onset diseases mean the gene can be passed on by either homozygotes or heterozygotes  Ex – Huntington disease - Sickle cell as an example o Multiple alleles – 400 mutant alleles o Pleiotropy – sickled cells have a lot of problems o Recessive lethality – many homozygotes of the recessive mutant allele die very early in life o Different dominance relations - Two genes can interact to determine one trait o Ex – lentils with seed coat color  Both dominant alleles – brown  One dominant allele – tan or gray (depending on which gene)  No dominant alleles – green  9 brown: 3 gray: 3 tan: 1 green (in F2 from pure breeding tan and gray)  F1 is brown  Each genotypic class determines a particular phenotype - Complementary gene action o Ex – white flowers give a purple F1  F2 selfing gives ratio of 9 purple: 7 white  Two genes work to create the purple flower so there has to be a dominant allele of both (A- B-) - Epistasis – gene interaction in which the effects of an allele at one gene hide the effects of alleles at another gene o Epistatic gene – allele doing the masking o Hypostatic gene – gene being masked o Ex – coat color in Labrador retrievers  A dominant B becomes black  A recessive bb homozygote is brown  Dominant E has no effect  Recessive ee homozygote is gold and hides any brown or black  9 black: 3 brown: 4 gold - Recessive epistasis – the allele causing the epistasis is recessive o Can be identified by F2 with ratio of 9:3:4 o Ex – the requirement of an ee homozygote to hide the effects of another gene - Dominant epistasis – the dominant allele of one gene hides the effects of another gene o Has phenotypic ratios of 12:3:1 or 13:3 o Ex- summer squash  B- is epistatic to any Aa genotype and produces white squase  bb is recessive to any Aa genotype  A- with bb gives yellow squash  aa with bb gives green squash  12 white: 3 yellow: 1 green o ex – feather color of leghorn chickens  13 white birds: 3 colored birds  For color there has to be at least one A and no B  B is epistatic to A - Table 3.2 – Gene interactions - Heterogeneous trait – mutation at any one of a number of genes that gives rise to the same phenotype o Ex – human deafness – 50 different genes can be have mutant alleles to cause deafness  Complementation – offspring receiving two mutations express the wild type phenotype  The original mutations affected two different genes and for both genes the normal allele from one parent can provide what the mutant allele of the other parent cannot  Wild type allele if parents are deaf but children can hear  Noncomplementation – the two mutations independently alter the same gene  Offspring receiving two recessive mutant alleles express the mutant phenotype  Homozygous Mutant alleles if parents are deaf and children are deaf - Complementation cannot be used if either mutation is dominant to the wild type - Genetic variations on the theme of multifactorial traits o Genes can interact to generate novel phenotypes o Dominant alleles of two interacting genes can both be necessary for the production of a particular phenotype o One gene’s alleles can mask effects of another’s o Mutant alleles at one of two or more different genes can result in the same phenotype  XY o Humans and flies – normal male  XO o Flies – sterile male o Humans – turner female (sterile), webbed neck  XYY o Flies – normal male o Humans – normal or almost normal male  Drosophila sex is mainly determined by the ratio of X chromosomes to autosomes o The presence of the Y chromosome is not a huge factor o Female – ratio is 1:1 o Males – ratio is 1:2 o The Y chromosome is needed for male fertility  Differences in human and drosophila sex determination o Genes they carry on their sex chromosomes are not identical o Strategies used to deal with presence of additional sex chromosomes are not the same  Chromatin – DNA and protein o Surrounded by nuclear envelope o Condenses into threads to become the chromosome  Nucleoli – chromatin involved in manufacturing ribosome’s  Chromatid – each rod making up a chromosome  Mitosis results in two daughter cells that are genetically identical to the parent cell  Cell cycle – pattern of cell growth followed by division  Interphase – period between division in the cell cycle  G0 – resting part of interphase when cells will not usually divide again o Ex – mature human brain cells  Centrosome – organizing center near the nuclear envelope where microtubules radiate out into the cytoplasm  Centrioles – core of each centrosome  Prophase – chromosomes gradually begin to differentiate to begin mitosis o Nucleoli begin to break down and disappear o Cell metabolism shuts down so the cell’s energy can be in chromosome movements and cellular division o Centrosomes move apart and become clearly distinguishable as separate entities  Go to opposite ends of the nucleus by microtubules  Prophase in meiosis o Critical events  Condensation of chromatin  Pairing of homologous chromosomes  Reciprocal exchange of genetic information o Page 98 – very in depth description o Synaptonemal complex – protein structure that aligns the homologs so corresponding genetic regions of the chromosome pair are lined up o Bivalent – synapsed chromosome pair with two chromosomes o Recombination nodules – structures along the synaptonemal complex that allow for exchange of partes between nonsister chromatids o Chiasmata – sites where crossing-over occurred  Checkpoints – moments at which the cell evaluates the results of previous steps and allow for sequential coordination of cell-cycle events  Meiosis = 1 round of chromosome replication and 2 rounds of nuclear division o Division I – parent nucleus divides to form two daughter nuclei  Centromeres that join chromatids stay intact during the whole division  Reductional division – the number of chromosomes is reduced to one-half the normal diploid number o Division II – each of the two daughter nuclei divides = 4 nuclei  Equational division – each daughter cell has the same number of chromosomes as the parental cell present at the beginning of this division o End result = 4 daughter cells that each have n number of chromosomes  Figure 4.13 – page 96 = meiosis  Crossing over results in recombination o Each chromosome pair may no longer be completely maternal or paternal  Nondisjunction – homologs of a chromosome pair do not segregate during meiosis I  Variation caused by independent assortment increases with the number of chromosomes in the genome  Aspects of meiosis that contribute to genetic diversity in a population o Matter of chance towards which pole paternal and maternal homologs of each bivalent migrate during meiosis I o Reshuffling of genetic information through crossing-over ensures a greater amount of genetic diversity in gametes  Table 4.3 – page 102 = compares meiosis and mitosis  Gametogenesis – gamete formation  Oogenesis – egg formation in humans o Meiosis I = secondary oocyte and polar body o Only one of the products of a single meiosis serves as a female gamete o Primary oocytes stay stuck in meiosis and a woman is born with all the oocytes she will ever produce o Ovulation – released oocyte continues through metaphase of meiosis II o If oocyte is fertilized – completes meiosis II  Spermatogenesis – production of sperm o Spermatogonia – germ cells in the male testes where spermatogenesis occurs o Meiosis produces 4 equivalent haploid spermatids that will become sperm  Evidence to support the chromosome theory of inheritance o Phenotype of sexual identity is associated with the inheritance of particular chromosomes o Events of mitosis, meiosis, and gametogenesis ensure a constant number of chromosomes in the somatic cells of a species o Inheritance of genes corresponds with inheritance of chromosomes in every detail o Transmission of particular chromosomes coincides with transmission of specific traits other than sex determination  Crisscross inheritance – males get trait from mom and daughters get trait from dad  Hemizygous – diploid cells have half the number of alleles carried by the female on her two X chromosomes o Ex – male drosophila for eye color gene  Table 4.5 – Pedigree patterns – study this  Sex-limited traits – affect a structure or process that is found in only one sex  Sex-inlfuenced traits – show up in both sexes but expression of traits may differ between the two sexes because of hormonal differences o Ex – pattern baldness CHAPTER 5  Genetic linkage – genes that travel together  Ways recombinant progeny can result – o Recombination of genes on the same chromosome during gamete formation o Independent assortment of genes on nonhomologous chromosomes  Farther apart genes are = greater probability of separation through recombination  Syntenic – located on the same gene  Dihybrid crosses with ratios different from 1:1:1:1 of F1 gametes indicate that two genes are on the same chromosome o Drosophila example with mutant eye color and body color o Males look like mother because phenotype reflects the genotype of the one X chromosome they got from her o If the Drosophila genes assort independently then the dihybrid F1 females should make 4 kinds of gametes with four combinations of genes on X  Ratio should be 1:1:1:1  Half parental types and half recombinant types o Counting male progeny tells if the ration is right because they get X from mom  Parental types – allele combinations seen in the original mother or father of the P generation  Recombinant types – reshuffling of allele combinations so the combination is not seen in the P generation parents of the F1 females  Parental classes – combinations originally present in the P generation  Numbers of parental and recombinant F2 progeny are equal in independent assortment o Doubly heterozygous F1 will make equal numbers of all 4 gamete types  Linked genes – when the number of F2 progeny with parental genotypes exceeds the number of F2 progeny with recombinant genotypes  Recombinants will not be as likely with alleles that are very tightly coupled  Linkage does not have to be really tight o Parentals = recombinants (RF=50%) o Occurs either when genes are on different chromosomes or when they are sufficiently far apart on the same chromosome  Recombination frequency (RF) – measure of the distance separating two genes along a chromosome  Two point crosses – crosses tracing two genes at a time  Problems with two point crosses o Difficult to determine gene order if some gene pairs lie close together o Actual distances in the map do not always add up o Ignores double crossovers that may occur in the large interval between the y and r genes  Three point crosses are more accurate than two point crosses o Look at pairs of genes and determine parental combinations and recombinant combinations o Determine distance apart by taking adding up amount of progeny for whichever traits are different than parentals and being compared/total progeny X 100  Use the ones that have the gene you are looking at switched o The genes with the longest distance will be on the outside and the other gene must be in the middle  Discrepancy in distances comes from rare double crossovers  Recombination takes place during prophase I  Have to establish the order of genes to determine where crossover events happen  Double crossovers generate gametes where the gene in the middle has recombined relative to the parental combinations for the genes at the end  Majority of offspring will be parental combinations  2 groups in the middle of middle sizes are from single crossover  2 smallest group = double crossover events o have to adjust recombination frequency by adding double crossovers twice to make distance more accurate  A number for a smaller distance is more accurate because there is less likely to be a double crossover than if it was a larger distance  Chromosomal interference – fact that the number of observed double crossovers is less than the number expected if the two exchanges are independent events = the occurrence of one crossover reduces the likelihood that another crossover will occur in an adjacent part of the chromosome o Crossovers no occurring independently o May make sure that each homologous pair has a crossover event because homologous chromosome pairs without crossovers tend to segregate wrong o Lowers number of crossovers on large chromosomes o Raises the probability of crossovers occurring on small chromosomes o Interference = 1- coefficient of coincidence  Coefficient of coincidence – ratio between the actual frequency of double crossovers observed in an experiment and the number of double crossovers expected on the basis of independent probabilities o Frequency observed/frequency expected o Provides a quantitative measure of the amount of interference in different chromosomal intervals  Interference = 0 o Frequency of observed double crossovers equals expectations o Crossovers in adjacent regions of a chromosome happen independently of each other  Interference = 1 (complete) o Coefficient of coincidence = 0 o No double crossovers occur in the experimental progeny because one exchange prevents another  In gametes formed by double crossovers – gene whose alleles have recombined relative to the parental configurations of the other two genes must be the one in the middle o Determined from a three point cross  Order of genes from mapping correlates with the order of those genes on the DNA molecule of a chromosome  Actual physical distances/amount of DNA separating genes does not show a correspondence to genetic map distances o Too much possibility of crossovers  Chromosomes will never recombine more than 50% of the time no matter how far apart they are  Recombination is not uniform over the length of a single chromosome o Hotspots – favored sites of recombination o Recombination deserts – areas (often near centromeres) where few crossovers ever happen  Recombination rates vary between species o Can also vary between males and females of a species  Ex – no recombination in male Drosophila  Linkage group – genes chained together by linkage relationships o Genes are syntenic if they can be linked together  Total genetic distance – sum of many short distances between genes  Pairwise crosses – between genes located at the two ends will not make more than 50% recombinant progeny  DNA marker – piece of DNA of known size, representing a specific locus and comes in identifiable variations  Fungi are good for genetic analysis because they hold the 4 haploid products of each meiosis in an ascus (sac) o Ascospores – haploid cells that can germinate and survive as viable haploid individuals that grow and perpetuate themselves with mitosis  Phenotype directly shows genotype o Haploid cells come in two mating types so sexual reproduction is possible  Cells of opposite mating types can fuse = diploid zygote  Stress can make diploid cells go into meiosis o Tetrad – assemblage of 4 ascospores in a single ascus after meiosis  Unordered – 4 meiotic products (spores) are arranged at random within the ascus  Ordered – 4 pairs or 8 haplospores arranged in a line  If conditions promote meiosis – the two unlinked genes will assort independently to produce equal frequencies of two different kinds of tetrads  Parental ditype (PD) – tetrad that contains 4 parental class haploid cells  Nonparental ditype (NPD) – tetrad that forms when the parental classes recombine to form two reciprocal nonparental combinations of alleles = contains 4 recombinant spores  Tetratype (T) – tetrad that appears when cells undergo meiosis and carries four kinds of haploid cells – two parental class and two recombinant class o Result of crossover between one of the two genes and the centromere of the chromosome it is located on  Classification is only based on number of parental and recombinant spores in the ascus  PD = NPD means that two genes are unlinked o Genes are either on different chromosomes or really far apart on the same chromosome  PD >>NPD means that two genes are linked  Linkage – emergence of more parental types than recombinants among the progeny of a doubly heterozygous parent  Double crossover involving two chromatids = both crossovers affect the same two chromatids o Produces parental-type progeny = PD tetrad o Double crossover can happen with 2-4 strands  No crossing over = parental ditype  Single crossover = tetratype  2-strand Double crossover = parental ditype  3-strand double crossover = tetratype  4-strand double crossover = nonparental ditype  Recombination frequency (RF) = NPD+ ½T / Total tetrads X 100 o Accurate for genes separated by small distances o Less reliable for more distant genes = doesn’t account for all types of double crossovers  Low number of NPD shows that recombination happens after the chromosomes have replicated when there are four chromatids for each pair of homologs o If before then more tetrads would have NPD instead of T  Meiotic recombination is almost always reciprocal = 2 homologous chromosomes that are inverted images of each other o Unusual ratios can exist but are quite rare o Recombination does not create new alleles  Ordered tetrads allow for mapping of the centromere of a chromosome relative to other genetic markers