Beyond Mendel s Laws of Inheritance

Transcription

1 Beyond Mendel s Laws of Inheritance

2 Extending Mendelian genetics Mendel worked with a simple system peas are genetically simple most traits are controlled by a single gene each gene has only 2 alleles, 1 of which is completely dominant to the other The relationship between genotype & phenotype is rarely that simple

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

4 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

5 Incomplete dominance P true-breeding red flowers X true-breeding white flowers 100% pink flowers F 1 generation (hybrids) 25% 50% self-pollinate 25% white 100% It s like flipping 2 pennies! red pink 1:2:1 F 2 generation

6 2 alleles affect the phenotype equally & separately not blended phenotype human ABO blood groups 3 alleles I A, I B, i I A & I B alleles are co-dominant glycoprotein antigens on RBC I A I B = both antigens are produced i allele recessive to both

7 Co-dominance 2 alleles affect the phenotype equally & separately not blended phenotype human ABO blood groups 3 alleles I A, I B, i I A & I B alleles are co-dominant glycoprotein antigens on RBC I A I B = both antigens are produced i allele recessive to both

8 Genetics of Blood type phenotype A B genotype I A I A or I A i I B I B or I B i antigen on RBC on surface of RBC on surface of RBC AB I A I B on surface of RBC O i i on surface of RBC antibodies in blood donation status universal recipient universal donor

9 Genetics of Blood type phenotype A B genotype I A I A or I A i I B I B or I B i antigen on RBC type A antigens on surface of RBC type B antigens on surface of RBC AB I A I B type B antigens on surface both type A & of RBC O i i no antigens on surface of RBC antibodies in blood anti-b antibodies anti-a antibodies no antibodies anti-a & anti-b antibodies donation status universal recipient universal donor

10 Most genes are pleiotropic one gene affects more than one phenotypic character 1 gene affects more than 1 trait dwarfism (achondroplasia) gigantism (acromegaly)

11 Pleiotropy Most genes are pleiotropic one gene affects more than one phenotypic character 1 gene affects more than 1 trait dwarfism (achondroplasia) gigantism (acromegaly)

12 Acromegaly: André the Giant

13 Inheritance pattern of Achondroplasia Aa x aa Aa x Aa a a A a A dwarf dwarf lethal dwarf A a a dwarf % dwarf: % normal or _: % dwarf: % normal or _:_

14 Inheritance pattern of Achondroplasia Aa x aa dominant inheritance a a Aa A x Aa a A Aa dwarf Aa dwarf A AA lethal Aa a aa aa a Aa aa 50% dwarf:50% normal or 1:1 67% dwarf:33% normal or 2:1

15 B_C_ bbc _cc One gene completely masks another gene coat color in mice = 2 separate genes C,c: 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!

16 B_C_ bbc _cc Epistasis One gene completely masks another gene coat color in mice = 2 separate genes C,c: 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!

17 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

18 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 eye color intelligence behaviors

19 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

20 Skin color: Albinism Johnny & Edgar Winter However albinism can be inherited as a single gene trait aa = albino albino Africans melanin = universal brown color enzyme tyrosine melanin albinism

21 OCA1 albino Bianca Knowlton oculocutaneous albinism (OCA)

22 Genes are on as opposed to autosomal chromosomes first discovered by T.H. Morgan at Columbia U. Drosophila breeding good genetic subject prolific 2 week generations 4 pairs of chromosomes XX=female, XY=male

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

24 Classes of chromosomes autosomal chromosomes sex chromosomes

25 Thomas Hunt Morgan in The Fly Room! (Columbia University 1910) Fruit Flies (Drosophila melanogaster)

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

27 What s up with Morgan s flies? x x RR rr Rr Rr r r R r R Rr Rr R Doesn t work that way! RR Rr R Rr Rr r Rr rr 100% red eyes 3 red : 1 white

28 Genetics of Sex 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 X XX Y XY 50% female : 50% male X XX XY

29 Let s reconsider Morgan s flies x x X R X R X R X r X R X r X r Y Y X R Y XRXr X R X R BINGO! X R X R XRY Y X R Y X R X R X r X R Y 100% red eyes X r X R X r X r Y 100% red females 50% red males; 50% white males

30 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

31 Human X chromosome Sex-linked usually means X-linked more than 60 diseases traced to genes on X chromosome Duchenne muscular dystrophy Becker muscular dystrophy 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 Immunodeficiency, X-linked, with hyper IgM Lymphoproliferative syndrome Albinism-deafness syndrome Fragile-X syndrome 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 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

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

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35 Contact with collagen fibres in blood vessels Factor XII (inactive) Factor XII (active) Factor III Thromboplastin released from blood vessel walls Factor XI (inactive) Factor XI (active) Factor VIII Antihemophilic factor A Factor IX (inactive) Factor IX (active) Antihemophilic factor B Ca 2+ ions and blood platelets Factor X (inactive) Factor X (active) Vitamin K precursor Factor II (inactive) Factor II (active) Prothrombin Thrombin 2007 Paul Billiet ODWS Factor I (inactive) Factor I (active) Fibrinogen Fibrin

36 Hemophilia About 85% of haemophiliacs suffer from classic haemophilia (1 male in ) cannot produce factor VIII The rest show Christmas disease where cannot make factor IX Genes for hemophilia are sex linked Hemophiliacs do clot their blood, but very slowly (there is an alternative pathway via thromboplastin) 2007 Paul Billiet ODWS

37 female / eggs Hemophilia sex-linked recessive XHh H X h x XHH H Y male / sperm X H Y X H X h X H X h X H Y carrier disease

38 female / eggs Hemophilia sex-linked recessive XHh H X h x XHH H Y male / sperm X H Y X H X h X H X h X H X h X H X H X H X h X H Y X h Y X H Y X H Y carrier disease

39 Daltonism = Red-Green Colorblindness Normal vision Colour blind simulation

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42 The retina LIGHT Optic nerve fibres Rod cell Cone cell Ganglion layer Bipolar cells (neurones) Synapse layer Nuclear layer Inner segments packed with mitochondria Rod and cone outer segments

43 PHOTORECEPTION VISION COLOUR MONOCHROME PHOTORECEPTOR CONES: red sensitive 560nm green sensitive 530nm blue sensitive 420nm RODS: max. sensitivity 505nm DISTRIBUTION Concentrated in the fovea Widely spread over whole retina, absent from fovea PIGMENTS 3 proteins controlled by 3 genes. Red and green pigments sex linked Blue pigment autosomal (Chr.7) RHODOPSIN = Retinol (Vit A) + Opsin (a protein). Also called visual purple BLEACHING Slow Fast (very sensitive) REGENERATION USE 2007 Paul Billiet ODWS Slow (after images in bright light, complementary colours) Daylight vision Light adaptation 5 min Fast Night vision Dark adaptation 20 min or wear red goggles!

44 Female mammals inherit 2 X chromosomes one X becomes inactivated during embryonic development condenses into compact object = which X becomes Barr body is random patchwork trait = mosaic X H X h X H X h

45 X-inactivation Female mammals inherit 2 X chromosomes one X becomes inactivated during embryonic development Meow. condenses into compact object = Barr body which X becomes Barr body is random patchwork trait = mosaic patches of black X H X h X H tricolor cats can only be female X h patches of orange

46 Fig Early embryo: Two cell populations in adult cat: Active X X chromosomes Allele for orange fur Allele for black fur Cell division and X chromosome inactivation Active X Inactive X Barr Body inactive X Black fur Orange fur visible in interphase nucleus

47 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

48 Environmental effects 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 is AP influenced Biology by soil ph

49 Any Questions?

50 Colorblind individuals see a yellow square. Color normal individuals see a yellow square and a faint brown circle.

51 Colorblind individuals see a number 17. Color normal individuals see a number 15.