* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download AP Inheritance
Site-specific recombinase technology wikipedia , lookup
Hybrid (biology) wikipedia , lookup
Ridge (biology) wikipedia , lookup
Transgenerational epigenetic inheritance wikipedia , lookup
Heritability of IQ wikipedia , lookup
Nutriepigenomics wikipedia , lookup
Genetic engineering wikipedia , lookup
Minimal genome wikipedia , lookup
Public health genomics wikipedia , lookup
Genome evolution wikipedia , lookup
Polymorphism (biology) wikipedia , lookup
Biology and consumer behaviour wikipedia , lookup
Neocentromere wikipedia , lookup
Pharmacogenomics wikipedia , lookup
Gene expression profiling wikipedia , lookup
Skewed X-inactivation wikipedia , lookup
Behavioural genetics wikipedia , lookup
Gene expression programming wikipedia , lookup
Y chromosome wikipedia , lookup
Medical genetics wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
History of genetic engineering wikipedia , lookup
Epigenetics of human development wikipedia , lookup
Population genetics wikipedia , lookup
Genomic imprinting wikipedia , lookup
Genetic drift wikipedia , lookup
X-inactivation wikipedia , lookup
Genome (book) wikipedia , lookup
Designer baby wikipedia , lookup
Hardy–Weinberg principle wikipedia , lookup
Microevolution wikipedia , lookup
Inheritance & Mendelian Genetics Gregor Mendel Modern genetics began in the mid-1800s in an abbey garden, where a monk named Gregor Mendel documented inheritance in peas used experimental method used quantitative analysis collected data & counted them Most traits in most species do not follow the simple Mendelian pattern, but it was a starting point Mendel’s work Bred pea plants Pollen transferred from white flower to stigma of purple flower P cross-pollinate true breeding parents (P) P = parental raised seed & then observed traits (F1) F = filial allowed offspring to self-pollinate & observed next generation (F2) anthers removed all purple flowers result F1 self-pollinate F2 What did Mendel’s findings mean? Traits come in alternative versions purple vs. white flower color alleles different alleles vary in the sequence of nucleotides at the specific locus (locus = location on a chromosome) of a gene some difference in sequence of A, T, C, G purple-flower allele & white-flower allele are two DNA variations at flower-color locus different versions of gene at same location on homologous chromosomes Traits are inherited as discrete units For each characteristic, an organism inherits 2 alleles, 1 from each parent diploid organism inherits 2 sets of chromosomes, 1 from each parent homologous chromosomes - same genetic loci (i.e. same genes), different alleles at those loci What did Mendel’s findings mean? Some traits “mask” others purple & white flower colors are separate traits that do not blend purple x white ≠ light purple purple masked white dominant allele functional protein masks other alleles wild type allele producing functional protein mutant allele producing malfunctioning protein recessive allele allele typically makes a malfunctioning protein homologous chromosomes Genotype vs. phenotype Difference between how an organism “looks” & its genetics phenotype description of an organism’s trait the “physical,” the result of gene expression genotype description of an organism’s genetic makeup Its combo of alleles, like “Pp” X P purple white F1 all purple Dominant ≠ most common allele Because an allele is dominant does not mean… it is more common, healthier, stronger, better, more likely, etc. Polydactyly dominant allele, yet rare! Making crosses Can represent alleles as letters flower color alleles P or p true-breeding purple-flower peas genotype PP true-breeding white-flower peas genotype pp In research, alleles are usually letter/number/symbol combinations (like ser83psE) X x P PP purple pp white Pp F1 all purple Discussion Which of these are phenotypes and which are genotypes? 1. Curly hair 2. Jj 3. PE1PE2 4. Arthritic knees 5. Type B blood 6. Spotted fur and a pink nose 7. HHGg 8. Purple leaves and spiny stem Punnett Square reminders The side and top boxes = parents’ potential gametes, each equally likely. Inner boxes = potential zygotes. Punnett Squares predict the odds of each offspring being born with a given genotype/phenotype. Does not ensure that, say, 50% of the children will definitely be freckled. Genotypes Homozygous = same alleles = PP, pp “True-breeding” = homozygous Heterozygous = different alleles = Pp “Carrier” homozygous dominant heterozygous homozygous recessive Test cross Method to determine genotype in case of dominant phenotype Breed the dominant phenotype with a homozygous recessive (pp) to determine the identity of the unknown allele How does that work? x is it PP or Pp? pp Discussion Suppose that the Y allele codes for orange fins and the y allele codes for yellow fins. The heterozygous genotype: __ The homozygous dominant genotype: __ The homozygous recessive genotype: __ A fish with yellow fins must have a _____________ genotype. A fish with orange fins could be either _____________ or ___________________. If a fish has orange fins, test-crossing it with a ______-finned fish will produce either 100% _____ or 50% orange/50% yellow. If the former result, the orange fish was _________. If the latter result, the orange fish was _________. Mendel’s 1st law of heredity Law of segregation P PP during meiosis, alleles segregate P homologous chromosomes separate each allele for a trait is packaged into a separate gamete You only give 1 allele per gene to your p pp child p P Pp p Law of Segregation Suppose there’s an eye color locus, with bb bb B BB Normal cell in G1 Meiosis II b b Meiosis I S Phase the alleles B for brown eyes or b for blue eyes. A man has the genotype Bb, which gives him the phenotype brown eyes. Meiosis produces his gametes… b B BB B Four Gametes He can make gametes that are EITHER B or b. Half of his gametes will be one, half will be the other. That’s segregation! Discussion Monohybrid cross practice! Show Punnett Squares to support your answer. If two black bees (bees A and B) have 676 babies, all black; two red bees (bees C and D) have 983 babies, all red; and a different two black bees (bees E and F) have 524 babies, 220 red and 304 black, what was each bee’s genotype? Use any letter for the alleles that you want. What generation were bees A,B,C,D,E, and F a part of? What generation were their children a part of? Dihybrid cross Other of Mendel’s experiments followed the inheritance of 2 different characters seed color and seed shape dihybrid crosses Mendel was working out many of the genetic rules! Dihybrid cross P true-breeding yellow, round peas Y = yellow R = round true-breeding green, wrinkled peas x YYRR yyrr y = green r = wrinkled yellow, round peas F1 100% generation (hybrids) YyRr self-pollinate F2 generation 9:3:3:1 9/16 yellow round peas 3/16 green round peas 3/16 yellow wrinkled peas 1/16 green wrinkled peas YyRr Dihybrid cross YR YyRr x YyRr YR Yr yR yr yr YR YYRR YYRr YyRR YyRr Yr YyRr Yyrr yR YyRR YyRr yyRR yyRr yr YYRr YyRr YYrr Yyrr yyRr yyrr or YyRr YR Yr yR yr 9/16 yellow round 3/16 green round 3/16 yellow wrinkled 1/16 green wrinkled Mendel’s 2nd law of heredity Law of independent assortment yellow different loci (genes) separate into gametes independently non-homologous chromosomes align independently green classes of gametes produced in equal amounts YR = Yr = yR = yr round wrinkled YyRr Yr Yr 1 yR : yR 1 YR : YR 1 yr : yr 1 Discussion Complete a Punnett Square for this dihybrid cross problem! If A = tall and a = short, while B = fuzzy and b = smooth… What are the odds that a parent heterozygous for both traits and a short smooth parent will have a tall and fuzzy offspring? Law of Independent Assortment EXCEPTION If genes are on same chromosome & close together will usually be inherited together rarely crossover separately “linked” Rules of Probability Probability scale ranges from 0 to 1 Rule of Multiplication: determine the chance that two or more independent events will occur together in some specific combination. Compute the probability of each independent event. Then, multiply the individual probabilities to obtain the overall probability of these events occurring together. Rule of Addition: probability of an event that can occur two or more different ways is the sum of the separate probabilities of those ways. Rules of Probability For instance, if I roll a six-sided die, what are the odds I’ll get a number that is equal to or less than 2? Which law did you use? If I roll two dice, what are the odds I’ll get a 1 both times? Which law did you use? Discussion You have been using both rules all along! How does the rule of multiplication come into play in a monohybrid cross? The rule of addition? Rules of Probability What are the odds that a homozygous red-haired, heterozygous green-eyed, white-chinned cat (AAEeww) and a dark-haired, heterozygous green-eyed, white-chinned cat (aaEeww) would have a kitten with the genotype AaEeww? We can solve each gene as a separate monohybrid problem, then multiply! Discussion AAEeww x aaEeww = ?% AaEeww Discussion Determine the probability of finding two recessive phenotypes for at least two of three traits resulting from a trihybrid cross between pea plants that are PpYyRr and Ppyyrr. There are five possible genotypes that fulfill this condition: ppyyRr, ppYyrr, Ppyyrr, PPyyrr, and ppyyrr. Hint: Use the rule of multiplication to calculate the probability for each of these genotypes, and then use the rule of addition to pool the five probabilities. Answer: The probability of producing a ppyyRr offspring: The probability of producing pp = 1/2 x 1/2 = 1/4. The probability of producing yy = 1/2 x 1 = 1/2. The probability of producing Rr = 1/2 x 1 = 1/2. Therefore, the probability of all three being present (ppyyRr) in one offspring is 1/4 x 1/2 x 1/2 = 1/16. For ppYyrr: 1/4 x 1/2 x 1/2 = 1/16. For Ppyyrr: 1/2 x 1/2 x 1/2 = 2/16 For PPyyrr: 1/4 x 1/2 x 1/2 = 1/16 For ppyyrr: 1/4 x 1/2 x 1/2 = 1/16 Therefore, the chance of at least two recessive traits is 6/16 = 3/8. Beyond Mendel’s Laws of Inheritance Mendel chose peas luckily Relatively simple genetically most characters are controlled by a single gene with each gene having only 2 alleles one completely dominant over the other All the genes he chose happened to be on different chromosomes - whew! Extending Mendelian genetics The inheritance of traits can rarely be explained by simple Mendelian genetics Various patterns of inheritance: incomplete dominance, codominance, pleiotropy, lethality, epistasis, polygenetic traits, multiallelic genes, sex-linked traits… Not all traits just determined by nuclear DNA: environmental effects, gene regulation, mitochondrial DNA… Incomplete dominance Heterozygote shows a NOVEL, intermediate, blended phenotype example: RR = red flowers RR rr = white flowers WW Rr = pink flowers RW make 50% less color RR RW WW Incomplete dominance P X true-breeding red flowers true-breeding white flowers 100% pink flowers F1 100% generation (hybrids) self-pollinate 25% red F2 generation 50% pink 25% white 1:2:1 Co-dominance 2 alleles affect the phenotype equally & separately Phenotype is not blended, it’s both of the true-breeding phenotypes simultaneously Speckled chickens, Roan cows, human ABO blood groups 3 alleles IA, IB, i IA & IB alleles are co-dominant glycoprotein antigens on RBC IAIB = both antigens are produced i allele recessive to both Genetics of Blood type phenogenotype type A B AB O antigen on RBC antibodies in blood donation status IA IA or IA i type A antigens on surface of RBC anti-B antibodies __ IB IB or IB i type B antigens on surface of RBC anti-A antibodies __ IA IB both type A & type B antigens on surface of RBC no antibodies universal recipient ii no antigens on surface of RBC anti-A & anti-B antibodies universal donor Pleiotropy Most genes are pleiotropic one gene affects more than one trait dwarfism (achondroplasia) Lethal pleiotropy Aa x aa Aa x Aa dominant inheritance A a a a Aa Aa achondroplastic achondroplastic aa aa typical typical 50% affected:50% typical or 1:1 A A a AA Aa lethal a Aa achondroplastic achondroplastic aa typical 67% affected:33% typical or 2:1 Discussion What if an allele is lethal recessive? Suppose that in a plant, the recessive allele for yellow seeds is lethal, the dominant allele for green seeds is not. What phenotypic ratios would you get from a cross of… GG x Gg? Gg x Gg? Gg x gg? (gg produced by genetically engineering gametes while leaving the somatic cells intact) Epistasis One gene completely masks another gene coat color in mice = 2 separate genes C,c: B_C_ bbC_ _ _cc pigment (C) or no pigment (c) B,b: more pigment (black=B) or less (brown=b) cc = albino, no matter B allele 9:3:3:1 becomes 9:3:4 How would you know that difference wasn’t random chance? Chi-square test! Epistasis in Labrador retrievers 2 genes: (E,e) & (B,b) pigment (E) or no pigment (e) pigment concentration: black (B) to brown (b) eebb eeB– E–bb E–B– Polygenic inheritance Some traits determined by additive effects of 2 or more genes phenotypes on a continuum human traits skin color height weight intelligence behaviors Skin color: Albinism However, albinism can be inherited as a single gene trait tyrosine aa = albino enzyme melanin albinism Sex linked traits Genes are on sex chromosomes as opposed to autosomal chromosomes first discovered by T.H. Morgan’s “Fly Lab” at Columbia U. Drosophila breeding good genetic subject prolific 2 week generations 4 pairs of chromosomes XX=female, XY=male Classes of chromosomes autosomal chromosomes sex chromosomes Discovery of sex linkage P F1 true-breeding red-eye female X true-breeding white-eye male 100% red eye offspring Huh! Sex matters?! generation (hybrids) F2 generation 100% red-eye female 50% red-eye male 50% white eye male Let’s reconsider Morgan’s flies… P x XR XR Xr XR F1 XR XR Xr XR Xr x F1 XrY XR Xr Y XRY XRY 100% red eyes XR BINGO! Xr XRY XR Y XR XR XRY XR Xr X rY F2 100% red females 50% red males; 50% white males Genes on sex chromosomes Y chromosome few genes other than SRY sex-determining region master regulator for maleness turns on genes for production of male hormones many effects = pleiotropy! X chromosome other genes/traits beyond sex determination mutations: hemophilia Duchenne muscular dystrophy color-blindness Human X chromosome Sex-linked Duchenne muscular dystrophy Becker muscular dystrophy usually means “X-linked” more than 60 diseases traced to genes on X chromosome Chronic granulomatous disease Retinitis pigmentosa-3 Norrie disease Retinitis pigmentosa-2 Ichthyosis, X-linked Placental steroid sulfatase deficiency Kallmann syndrome Chondrodysplasia punctata, X-linked recessive Hypophosphatemia Aicardi syndrome Hypomagnesemia, X-linked Ocular albinism Retinoschisis Adrenal hypoplasia Glycerol kinase deficiency Ornithine transcarbamylase deficiency Incontinentia pigmenti Wiskott-Aldrich syndrome Menkes syndrome Androgen insensitivity Sideroblastic anemia Aarskog-Scott syndrome PGK deficiency hemolytic anemia Anhidrotic ectodermal dysplasia Agammaglobulinemia Kennedy disease Pelizaeus-Merzbacher disease Alport syndrome Fabry disease Immunodeficiency, X-linked, with hyper IgM Lymphoproliferative syndrome Albinism-deafness syndrome Fragile-X syndrome Charcot-Marie-Tooth neuropathy Choroideremia Cleft palate, X-linked Spastic paraplegia, X-linked, uncomplicated Deafness with stapes fixation PRPS-related gout Lowe syndrome Lesch-Nyhan syndrome HPRT-related gout Hunter syndrome Hemophilia B Hemophilia A G6PD deficiency: favism Drug-sensitive anemia Chronic hemolytic anemia Manic-depressive illness, X-linked Colorblindness, (several forms) Dyskeratosis congenita TKCR syndrome Adrenoleukodystrophy Adrenomyeloneuropathy Emery-Dreifuss muscular dystrophy Diabetes insipidus, renal Myotubular myopathy, X-linked Discussion Hemophilia is X-linked recessive. If a carrier and her healthy (unaffected) husband have a child, what are the odds that their child will be: Healthy? Hemophiliac? A carrier? X-inactivation Female mammals inherit 2 X chromosomes one X becomes inactivated during embryonic development condenses into compact object = Barr body which X becomes Barr body is random patchwork trait = “mosaic” patches of black XH XH Xh tricolor cats can only be female Xh patches of orange Male pattern baldness Sex influenced trait autosomal trait influenced by sex hormones age effect as well = onset after 30 years old dominant in males & recessive in females B_ = bald in males; bb = bald in females Environmental effects Phenotype is controlled by both environment & genes Human skin color is influenced by both genetics & environmental conditions Color of Hydrangea flowers is influenced by soil pH Coat color in arctic fox influenced by heat sensitive alleles Pedigrees 1 3 4 2 5 6 Pedigree analysis Pedigree analysis reveals Mendelian patterns in human inheritance = male data mapped on a family tree = female = male w/ trait = female w/ trait Studying Human Genetics Circle – female Square – male Shaded – afflicted with trait Half shaded or Dot – carrier Horizontal line – mating “marriage line” “sibling line” Vertical line – children Dotted vertical line - adopted children (Diagonal lines – twins) Discussion Draw a pedigree of your immediate family (if adopted, draw your choice of relatives) Pedigrees Pedigree analysis can reveal the inheritance pattern of the trait under consideration… Autosomal Dominant Autosomal dominant – allele is dominant and on an autosomal chromosome Every person with the trait, also had a parent with it. Not necessarily a child with it, though! Why? Autosomal Recessive Autosomal Recessive - allele is recessive and on an autosomal chromosome Trait only appears when two alleles are present, so there can be carriers. Trait often “skips” several generations or shows up seemingly out of nowhere. Why? X-linked Recessive X-linked Recessive – allele is recessive and is located on the X chromosome Males are more likely to show trait – Why? Skips generations X-linked Dominant X-linked Dominant - allele is dominant and is located on the X chromosome An afflicted father’s daughters will all be afflicted too – Why? No male to male transmission No skipped generations Y-Linked Y-Linked (recessive vs dominant doesn’t matter): Locus is on the Y chromosome Only males have it, and all sons of an affected male are also affected – Why? What’s the likely inheritance pattern? Label genotypes using A/a Discussion 11 33 44 22 55 66 Genetic counseling Pedigree can help us understand the past & predict the future Thousands of genetic disorders are inherited as simple recessive traits from benign conditions to deadly diseases albinism cystic fibrosis Tay sachs sickle cell anemia PKU Genetic testing sequence individual genes Tay-Sachs (recessive) Great example of how pedigrees and genetic counseling have made a difference! Primarily Jews of eastern European (Ashkenazi) descent & Cajuns (Louisiana) strikes 1 in 3600 births 100 times greater than incidence among non-Jews non-functional enzyme fails to breakdown lipids in brain cells fats collect in cells destroying their function symptoms begin few months after birth seizures, blindness & degeneration of muscle & mental performance child usually dies before age 5 Tay-Sachs Israel became the 1st country to offer free genetic testing to couples, in large part to eliminate TSD Haredi communities in the US often required couples to be tested before marriage Incidence of TSD declined by 90%! Before 1970, 50-70 Ashkenazi infants born with TSD per year in US By 2000s, only 1 or 2 per decade Non-Nuclear Inheritance Not all eukaryotic genes are in the nucleus! Found in mitochondria, plastids In animals, all cytoplasmic (non-nuclear) genes come from which parent, maternal or paternal? Randomly assorted to gametes and daughter cells Therefore, traits determined by plastid DNA and mtDNA do NOT display Mendelian inheritance Non-Nuclear Inheritance In humans, mitochondrial DNA (mtDNA) encodes mostly mitochondrial proteins (such as ETC proteins, mt-ribosomes) Mutations cause mitochondrial disorders, including lactic acidosis, some myopathies (muscle disorders)