Sex linked traits n 1910 1933 Genes are

Sex linked traits n 1910 | 1933 Genes are on sex chromosomes u u u as opposed to autosomal chromosomes first discovered by T. H. Morgan at Columbia U. Drosophila breeding n AP Biology good genetic subject w prolific w 2 week generations w 4 pairs of chromosomes w XX=female, XY=male

Classes of chromosomes autosomal chromosomes sex chromosomes AP Biology

Discovery of sex linkage P F 1 true-breeding red-eye female X true-breeding white-eye male 100% red eye offspring Huh! Sex matters? ! generation (hybrids) F 2 generation AP Biology 100% red-eye female �� 50% red-eye male 50% white eye male

What’s up with Morgan’s flies? x RR r R x Rr rr Rr R R Rr r RR Rr Rr rr Doesn’t work that way! R AP Biology Rr Rr 100% red eyes r 3 red : 1 white

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

Let’s reconsider Morgan’s flies… x X RX R Xr XR XR AP Biology X RX r x X r. Y Y X RY 100% red eyes XR BINGO! Xr X RX r X RY XR Y X RX R X RY X RX r X r. Y 100% red females 50% red males; 50% white males

Genes on sex chromosomes n Y chromosome u few genes other than SRY sex-determining region n master regulator for maleness n turns on genes for production of male hormones w many effects = pleiotropy! n n X chromosome u other genes/traits beyond sex determination n AP Biology mutations: w hemophilia w Duchenne muscular dystrophy

Human X chromosome n Sex-linked usually means “X-linked” u more than 60 diseases traced to genes on X chromosome u Duchenne muscular dystrophy Becker muscular dystrophy Chronic granulomatous disease Retinitis pigmentosa-3 Norrie disease Retinitis pigmentosa-2 Hypophosphatemia Aicardi syndrome Hypomagnesemia, X-linked Ocular albinism Retinoschisis Adrenal hypoplasia Glycerol kinase deficiency Ornithine transcarbamylase deficiency Incontinentia pigmenti Wiskott-Aldrich syndrome Menkes syndrome 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 Ig. M Lymphoproliferative syndrome Albinism-deafness syndrome Fragile-X syndrome AP Biology Ichthyosis, X-linked Placental steroid sulfatase deficiency Kallmann syndrome Chondrodysplasia punctata, X-linked recessive Androgen insensitivity 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 G 6 PD 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

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

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sex-linked recessive Hemophilia HX h x X HY HH XHh XH female / eggs male / sperm XH Xh AP Biology XH Y X HX H X HY X HX h Xh XH X HX h X h. Y carrier disease X HY Y

X-inactivation n Female mammals inherit 2 X chromosomes u one X becomes inactivated during embryonic development condenses into compact object = Barr body n which X becomes Barr body is random n w patchwork trait = “mosaic” patches of black X HX h tricolor cats can only be AP Biology female Xh patches of orange

Male pattern baldness n Sex influenced trait u autosomal trait influenced by sex hormones n u dominant in males & recessive in females n AP Biology age effect as well = onset after 30 years old B_ = bald in males; bb = bald in females

Environmental effects n Phenotype is controlled by both�� environment & genes Human skin color is influenced by both genetics & environmental conditions Coat color in arctic fox influenced by heat sensitive alleles Color of Hydrangea flowers APinfluenced Biology is by soil p. H

Any Questions? AP Biology 2006 -2007

Human Genetic Diseases 1 AP Biology 3 4 2 5 2006 -2007 6

Pedigree analysis n Pedigree analysis reveals Mendelian patterns in human inheritance u = male AP Biology data mapped on a family tree = female = male w/ trait = female w/ trait

Simple pedigree analysis 11 33 AP Biology 44 What’s the likely inheritance pattern? 22 55 66

Genetic counseling Pedigree can help us understand the past & predict the future n Thousands of genetic disorders are inherited as simple recessive traits n u from benign conditions to deadly diseases albinism n cystic fibrosis n Tay sachs n sickle cell anemia n PKU n AP Biology

Genetic testing sequence individual genes AP Biology

Recessive diseases n The diseases are recessive because the allele codes for either a malfunctioning protein or no protein at all u Heterozygotes (Aa) n n AP Biology carriers have a normal phenotype because one “normal” allele produces enough of the required protein

Heterozygote crosses n Heterozygotes as carriers of recessive alleles Aa x Aa female / eggs male / sperm A a AP Biology A a AA AA Aa Aa A Aa a carrier Aa Aa aa carrier disease A Aa a

Cystic fibrosis (recessive) n Primarily whites of European descent u strikes 1 in 2500 births n u n n AP Biology normal lung tissue normal allele codes for a membrane protein that transports Cl- across cell membrane n u 1 in 25 whites is a carrier (Aa) defective or absent channels limit transport of Cl- & H 2 O across cell membrane thicker & stickier mucus coats around cells mucus build-up in the pancreas, lungs, digestive tract & causes bacterial infections without treatment children die before 5; with treatment can live past their late 20 s

Chloride channel Effect on Lungs normal lungs airway Cl– transports salt through protein channel out of cell Osmosis: H 2 O follows Cl– channel H 2 O cells lining lungs cystic fibrosis Cl– H 2 O bacteria & mucus build up thickened mucus hard to secrete AP Biology mucus secreting glands

delta F 508 loss of one amino acid AP Biology

Tay-Sachs (recessive) n Primarily Jews of eastern European (Ashkenazi) descent & Cajuns (Louisiana) u strikes 1 in 3600 births n u non-functional enzyme fails to breakdown lipids in brain cells n n AP Biology 100 times greater than incidence among non-Jews fats collect in cells destroying their function symptoms begin few months after birth seizures, blindness & degeneration of muscle & mental performance child usually dies before 5 yo

Sickle cell anemia (recessive) n Primarily u Africans strikes 1 out of 400 African Americans n high frequency caused by substitution of a single amino acid in hemoglobin u when oxygen levels are low, sickle-cell hemoglobin crystallizes into long rods u deforms red blood cells into sickle shape n sickling creates pleiotropic effects = cascade of other symptoms n AP Biology

Sickle cell anemia n Substitution of one amino acid in polypeptide chain AP Biology hydrophilic amino acid hydrophobic amino acid

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Sickle cell phenotype n 2 alleles are codominant both normal & mutant hemoglobins are synthesized in heterozygote (Aa) u 50% cells sickle; 50% cells normal u carriers usually healthy u sickle-cell disease triggered under blood oxygen stress u n AP Biology exercise

Heterozygote advantage n Malaria u n single-celled eukaryote parasite spends part of its life cycle in red blood cells In tropical Africa, where malaria is common: u u u homozygous dominant individuals die of malaria homozygous recessive individuals die of sickle cell anemia heterozygote carriers are relatively free of both n n reproductive advantage High frequency of sickle cell allele in African Americans is vestige of African roots AP Biology

Prevalence of Malaria Prevalence of Sickle Cell Anemia AP Biology

Huntington’s chorea (dominant) n Dominant inheritance u Testing… Would you want to know? u repeated mutation on end of chromosome 4 n n n mutation = CAG repeats glutamine amino acid repeats in protein one of 1 st genes to be identified build up of “huntingtin” protein in brain causing cell death n n AP Biology 1872 memory loss muscle tremors, jerky movements w “chorea” starts at age 30 -50 early death w 10 -20 years after start

Genetics & culture n Why do all cultures have a taboo against incest? u n laws or cultural taboos forbidding marriages between close relatives are fairly universal Fairly unlikely that 2 unrelated carriers of same rare harmful recessive allele will meet & mate u u AP Biology but matings between close relatives increase risk n “consanguineous” (same blood) matings individuals who share a recent common ancestor are more likely to carry same recessive alleles

A hidden disease reveals itself Aa AA x Aa A AA AA a Aa Aa AP Biology female / eggs A Aa male / sperm A x A a A AA Aa aa • increase carriers in population • hidden disease is revealed

Any questions? AP Biology 2006 -2007

Ghosts of Lectures Past (storage) AP Biology 2006 -2007

Heterozygote advantage n Sickle cell frequency u high frequency of heterozygotes is unusual for allele with severe detrimental effects in homozygotes n n 1 out of 400 African Americans Suggests some selective advantage of being heterozygous sickle cell: resistance to malaria? u cystic fibrosis: resistance to cholera? u AP Biology

Malaria AP Biology

Woody Guthrie & Arlo Guthrie AP Biology