Beyond Mendel’s Laws of Inheritance 2006-2007

Incomplete dominance Heterozygote shows an intermediate, blended phenotype example: RR = red flowers rr = white flowers Rr = pink flowers make 50% less color RR WW RW RR RW WW

Co-dominance 2 alleles affect the phenotype equally & separately not blended phenotype 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 A IA IA or IA i B IB IB or IB i AB IA IB O i i pheno-type genotype antigen on RBC antibodies in blood donation status A IA IA or IA i type A antigens on surface of RBC anti-B antibodies __ B IB IB or IB i type B antigens on surface of RBC anti-A antibodies AB IA IB both type A & type B antigens on surface of RBC no antibodies universal recipient O i i no antigens on surface of RBC anti-A & anti-B antibodies universal donor

Polygenic inheritance Some phenotypes determined by additive effects of 2 or more genes on a single character phenotypes on a continuum human traits skin color height weight intelligence behaviors

Sex linked traits Genes are on sex chromosomes as opposed to autosomal chromosomes

Classes of chromosomes autosomal chromosomes sex chromosomes

Genetics of Sex X Y X XX XY X XX XY In humans & other mammals, there are 2 sex chromosomes: X & Y 2 X chromosomes develop as a female: XX gene redundancy, like autosomal chromosomes an X & Y chromosome develop as a male: XY no redundancy X Y X XX XY X XX XY 50% female : 50% male

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 Duchenne muscular dystrophy affects one in 3,500 males born in the United States. Affected individuals rarely live past their early 20s. This disorder is due to the absence of an X-linked gene for a key muscle protein, called dystrophin. The disease is characterized by a progressive weakening of the muscles and loss of coordination.

Human X chromosome Sex-linked usually means “X-linked” Duchenne muscular dystrophy Becker muscular dystrophy 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 Incontinentia pigmenti Wiskott-Aldrich syndrome Menkes 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 Androgen insensitivity Chronic granulomatous disease Retinitis pigmentosa-3 Norrie disease Retinitis pigmentosa-2 Sideroblastic anemia Aarskog-Scott syndrome PGK deficiency hemolytic anemia Anhidrotic ectodermal dysplasia Agammaglobulinemia Kennedy disease Pelizaeus-Merzbacher disease Alport syndrome Fabry disease Albinism-deafness syndrome Fragile-X syndrome Immunodeficiency, X-linked, with hyper IgM Lymphoproliferative syndrome Ornithine transcarbamylase deficiency Human X chromosome Sex-linked usually means “X-linked” more than 60 diseases traced to genes on X chromosome

Map of Human Y chromosome? < 30 genes on Y chromosome Sex-determining Region Y (SRY) linked Channel Flipping (FLP) Catching & Throwing (BLZ-1) Self confidence (BLZ-2) note: not linked to ability gene Devotion to sports (BUD-E) Addiction to death & destruction movies (SAW-2) Scratching (ITCH-E) Spitting (P2E) Inability to express affection over phone (ME-2) Selective hearing loss (HUH) Total lack of recall for dates (OOPS) Air guitar (RIF)

Hemophilia XHXh XHY Hh x HH XH XHXh XH Y Xh XHXH XHXH XHY XHY XH Xh XH sex-linked recessive Hemophilia XHXh XHY Hh x HH XH XHXh XH Y male / sperm Xh XHXH XHXH XHY XHY XH Xh female / eggs XH XHY XHXh XHXh XhY XhY Y carrier disease

Hemophilia is a sex-linked recessive trait defined by the absence of one or more clotting factors. These proteins normally slow and then stop bleeding. Individuals with hemophilia have prolonged bleeding because a firm clot forms slowly. Bleeding in muscles and joints can be painful and lead to serious damage. Individuals can be treated with intravenous injections of the missing protein.

X-inactivation Female mammals inherit 2 X chromosomes XH XHXh Xh 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 XHXh Xh tricolor cats can only be female patches of orange

Environmental effects Phenotype is controlled by both environment & genes Human skin color is influenced by both genetics & environmental conditions The relative importance of genes & the environment in influencing human characteristics is a very old & hotly contested debate a single tree has leaves that vary in size, shape & color, depending on exposure to wind & sun for humans, nutrition influences height, exercise alters build, sun-tanning darkens the skin, and experience improves performance on intelligence tests even identical twins — genetic equals — accumulate phenotypic differences as a result of their unique experiences Coat color in arctic fox influenced by heat sensitive alleles Color of Hydrangea flowers is influenced by soil pH

What are linked genes? There are more genes in a cell than there are chromosomes in a cell What does that mean? Each chromosome contains MANY genes Genes that are close together on the same chromosome tend to be inherited TOGETHER = linked genes

Genetic Recombination Independent assortment of chromosomes and crossing over produce genetic recombinants Genetic recombination Production of offspring with new combinations of traits different from those combinations found in parents Results from events of meiosis and random fertilization

Linked Genes Tend to be inherited together since they are located on the same chromosome Do not assort independently

F1 Generation of Linked genes: Looks normal so far... All of F1 offspring show dominant traits

When F1 generation is test crossed (mated with homozygous recessive), we would expect 1:1:1:1 ratio

Results of Morgan’s testcross Wild type Double mutant Gray body Normal Wings Black Body Vestigal Wings P b+b+ vg+vg+ bb vgvg

P X F1 bb vgvg b+b+ vg+vg+ Black Body Gray body Vestigal Wings Wild type Double mutant bb vgvg b+b+ vg+vg+ P Testcross Black Body Vestigal Wings Gray body Normal wings X F1 bb vgvg b+b vg+vg

F1 X F2 Expected Observed Gray body Normal wings Black Body Testcross Black Body Vestigal Wings F1 X b+b vg+vg bb vgvg F2 Gray Normal Black Vestigal Gray Vestigal Black Normal b+b vg+vg bb vgvg b+b vgvg bb vg+vg Expected 575 575 575 575 Observed 965 944 206 185

F1 X Recombinants Parentals F2 Expected Observed Gray body Normal wings Testcross Black Body Vestigal Wings F1 X b+b vg+vg bb vgvg Recombinants Parentals F2 Gray Normal Black Vestigal Gray Vestigal Black Normal b+b vg+vg bb vgvg b+b vgvg bb vg+vg Expected 575 575 575 575 Observed 965 944 206 185

Results of testcross b b vg+ vg b+ b vg+ vg b b vg vg b+ b vg vg Phenotypes Genotypes Expected results if genes are unlinked Expected results if genes are totally linked Actual results Black normal b b vg+ vg Gray normal b+ b vg+ vg Black vestigial b b vg vg Gray vestigial b+ b vg vg

Results of testcross b b vg+ vg 575 b+ b vg+ vg b b vg vg b+ b vg vg Phenotypes Genotypes Expected results if genes are unlinked Expected results if genes are totally linked Actual results Black normal b b vg+ vg 575 Gray normal b+ b vg+ vg Black vestigial b b vg vg Gray vestigial b+ b vg vg

Results of testcross b b vg+ vg 575 b+ b vg+ vg 1150 b b vg vg Phenotypes Genotypes Expected results if genes are unlinked Expected results if genes are totally linked Actual results Black normal b b vg+ vg 575 Gray normal b+ b vg+ vg 1150 Black vestigial b b vg vg Gray vestigial b+ b vg vg

Results of testcross b b vg+ vg 575 206 b+ b vg+ vg 1150 965 b b vg vg Phenotypes Genotypes Expected results if genes are unlinked Expected results if genes are totally linked Actual results Black normal b b vg+ vg 575 206 Gray normal b+ b vg+ vg 1150 965 Black vestigial b b vg vg 944 Gray vestigial b+ b vg vg 185

If 50% of offspring are recombinants of parentals 2 genes are on different chromosomes (not linked) it is expected result if 2 genes assort independently If there is a high proportion of parental phenotypes linkage between genes is likely

Recombination frequency Total number of flies observed 965 + 944 + 206 + 185 = 2300 Total number of recombinant flies 206 + 185 = 391 Recombinant frequency 391 ÷ 2300 = .17 .17 x 100 = 17%

17% of Morgan’s flies were recombinants linkage is probably incomplete Some mechanism occasionally breaks linkage between two genes Crossing over during meiosis accounts for recombination of linked genes

Using Recombination Frequencies to construct Chromosome Map Recombination frequencies between genes help map sequence of linked genes on particular chromosomes Morgan’s Drosophila studies showed some genes linked more tightly than others Recombination frequency between b and vg loci = 17% Recombination frequency between b and cn = 9% If crossing over occurs randomly, probability of crossing over between two genes is directly proportional to distance between them One map unit = 1% recombination frequency Map units are called centimorgans

Establish relative distance between genes farthest apart or with highest recombination frequency Consider two possible placements of 3rd gene

Results of this cross are shown below: Phenotype Genotype Observed # In Drosophila, curled wings and dark bodies are mutant traits. In a dihybrid testcross, a curled winged, dark bodied fly was crossed with a heterozygous normal bodied, normal winged fly. Results of this cross are shown below: Phenotype Genotype Observed # Curled, dark cucu ee 389 Normal, normal cu+cy e+e 414 Curled, normal cucu e+e 104 Normal, dark cu+cu ee 93 AP Biology

Identify the parentals and recombinants Phenotype Genotype Observed # Curled, dark cucu ee 389 Normal, normal cu+cy e+e 414 Curled, normal cucu e+e 104 Normal, dark cu+cu ee 93 AP Biology

Identify the parentals and recombinants Calculate recombinant frequency Phenotype Genotype Observed # Curled, dark cucu ee 389 Normal, normal cu+cy e+e 414 Curled, normal cucu e+e 104 Normal, dark cu+cu ee 93 AP Biology

Identify the parentals and recombinants Calculate recombinant frequency 104 + 93 = 197 (197÷1000) x 100 = 19.7 Calculate map units between two genes Phenotype Genotype Observed # Curled, dark cucu ee 389 Normal, normal cu+cy e+e 414 Curled, normal cucu e+e 104 Normal, dark cu+cu ee 93 AP Biology

Identify the parentals and recombinants Calculate recombinant frequency 104 + 93 = 197 (197÷1000) x 100 = 19.7 Calculate map units between two genes Map units = 19.7 Phenotype Genotype Observed # Curled, dark cucu ee 389 Normal, normal cu+cy e+e 414 Curled, normal cucu e+e 104 Normal, dark cu+cu ee 93 AP Biology