Topic 4.3 Theoretical Genetics

Definitions

Yellow pea plants must be heterozygous. The yellow phenotype is expressed. Segregation Through meiosis and fertilization, some offspring peas are homozygous recessive – they express a green color.

Genotype: Gametes: Punnett square: Genotypes: Phenotypes: Phenotype Ratio: F Monohybrid Cross Crossing a single trait F

Genotype: Gametes: Punnett square: Genotypes: Phenotypes: Phenotype Ratio: F Monohybrid Cross Crossing a single trait F Key to alleles: Y = yellow y = green

Genotype: Gametes: Punnett square: Genotypes: Phenotypes: Phenotype Ratio: F Monohybrid Cross Crossing a single trait F Key to alleles: Y = yellow y = green

Genotype: Gametes: Punnett square: Genotypes: Phenotypes: Phenotype Ratio: F Monohybrid Cross Crossing a single trait F Key to alleles: Y = yellow y = green

Key to alleles: R = red flower r = white Test Cross – used to determine the genotype of an unknown individual. The unknown is crossed with a known homozygous recessive Phenotype: Genotype: Phenotypes: Unknown parent = RR Unknown parent = Rr F F Possible Outcomes:

Is PKU dominant or recessive? How do you know? Phenylkentonuria (PKU)

Phenylketonuria (PKU) is a rare condition in which a baby is born without the ability to properly break down an amino acid called phenylalanine. It is a recessive mis-sense mutation.

Key to alleles: T = has enzyme t = no enzyme Pedigree Charts

Key to alleles: T = has enzyme t = no enzyme

Pedigree Chart Practice Dominant or Recessive? - Dominant: A and B are both affected but have produced an unaffected D and F, therefore A and B must be carrying healthy recessive alleles. Autosomal or Sex Linked? - Autosomal: Male C can only pass on one X chromosome. If it were carried on X then daughter H would be affected as well. affected Not affected decease d Female Male

MULTIPLE ALLELES Genes which have more than two alleles © 2007 Paul Billiet ODWSODWS

Genes and their alleles About 30% of the genes in humans are di-allelic, that is they exist in two forms, (they have two alleles) About 70% are mono-allelic, they only exist in one form and they show no variation A very few are poly-allelic having more than two forms © 2007 Paul Billiet ODWSODWS

Combinations Di-allelic genes can generate 3 genotypes Genes with 3 alleles can generate 6 genotypes (3+2+1) Genes with 4 alleles can generate 10 genotypes Genes with 8 alleles can generate 36 genotypes © 2007 Paul Billiet ODWSODWS

Genes and the immune system Poly-allelic alleles are usually associated with tissue types These genes are so varied that they provide us with our genetic finger print This is very important to our immune system which must tell the difference between our own cells (self) and invading disease causing microbes (non-self) © 2007 Paul Billiet ODWSODWS

The ABO blood system This is a controlled by a tri-allelic gene It can generate 6 genotypes The alleles control the production of antigens on the surface of the red blood cells Two of the alleles are codominant to one another and both are dominant over the third Allele I A produces antigen A Allele I B produces antigen B Allele i produces no antigen © 2007 Paul Billiet ODWSODWS

The ABO blood system GenotypesPhenotypes (Blood types) I A A I A I B AB IAiIAiA I B B IBiIBiB iiO Note: Blood types A and B have two possible genotypes – homozygous and heterozygous. Blood types AB and O only have one genotype each. © 2007 Paul Billiet ODWSODWS

Blood types and transfusions Blood types vary and your immune system recognises your own blood type as being self Other blood types are recognised as non-self If a blood which is incompatible with your body is transfused it will result in the agglutination of the foreign red blood cells © 2007 Paul Billiet ODWSODWS

Antigens © Biology Labs Online © Bioformatica

Agglutination © Dr Delphine Grézel, Ecole Nationale Vétérinaire de Lyon

Blood types and transfusions People who are Type A blood produce antibodies to agglutinate cells which carry Type B antigens They recognise them as non-self The opposite is true for people who are Type B Neither of these people will agglutinate blood cells which are Type O Type O cells do not carry any antigens for the ABO system Type O cells pass incognito What about type AB people? © 2007 Paul Billiet ODWSODWS

Donor-recipient compatibility Recipient TypeABABO A DonorB AB O = Agglutination = Safe transfusion Note: Type O blood may be transfused into all the other types = the universal donor. Type AB blood can receive blood from all the other blood types = the universal recipient. © 2007 Paul Billiet ODWSODWS

SEX LINKAGE Characters which are associate more with one gender © 2007 Paul Billiet ODWSODWS

Characters associated with gender Anhiorotic ectodermal dysplasia Small teeth, no sweat glands, sparse body hair Occurs primarily in men Never transmitted from father to son Unaffected daughters may pass the condition onto their sons (the grandsons) © 2007 Paul Billiet ODWSODWS

Sex linkage explained Thomas Hunt Morgan in The Fly Room! (Columbia University 1910) Fruit Flies (Drosophila melanogaster) © 2007 Paul Billiet ODWSODWS

The case of the white-eyed mutant CharacterTraits Eye colourRed eye (wild type) White eye (mutant) P Phenotypes Wild type (red-eyed) female x White-eyed male F 1 Phenotypes All red-eyed Red eye is dominant to white eye © 2007 Paul Billiet ODWSODWS

Hypothesis A cross between the F 1 flies should give us: 3 red eye : 1 white eye F2F2 PhenotypesRed eyeWhite eye Numbers % % So far so good © 2007 Paul Billiet ODWSODWS

An interesting observation F2F2 PhenotypesRed- eyed males Red- eyed females White- eyed males White- eyed females Numbers %58%18%0% © 2007 Paul Billiet ODWSODWS

A reciprocal cross Morgan tried the cross the other way around white-eyed female x red-eyed male Result All red-eyed females and all white-eyed males This confirmed what Morgan suspected The gene for eye colour is linked to the X chromosome © 2007 Paul Billiet ODWSODWS

A test cross PhenotypesF1 Red-eyed female x White-eyed male Expected result 50% red-eyed offspring: 50% white-eyed offspring Regardless of the sex Observed Results Red-eyed Males Red-eyed Females White-eyed Males White-eyed Females © 2007 Paul Billiet ODWSODWS

Genetic diagram for sex linked genes CharacterTraitAlleles Eye colourRed eyeR White eyer GenotypesPhenotypes XRXRXRXrXrXrXRXRXRXrXrXr XRYXrYXRYXrY © 2007 Paul Billiet ODWSODWS

Genetic diagrams for sex linked genes CharacterTraitAlleles Eye colourRed eyeR White eyer GenotypesPhenotypes XRXRXRXrXrXrXRXRXRXrXrXr Red-eyed female White-eyed female XRYXrYXRYXrY Red-eyed male White-eyed male © 2007 Paul Billiet ODWSODWS

PPhenotypesWild type (red-eyed) female xWhite-eyed male GenotypesXRXRXRXR XrYXrY GametesXRXR XRXR XrXr Y FertilisationXrXr Y XRXR XRXrXRXr XRYXRY XRXR XRXrXRXr XRYXRY © 2007 Paul Billiet ODWSODWS

F1F1 PhenotypesRed-eyed female xRed-eyed male GenotypesXRXrXRXr XRYXRY GametesXRXR XrXr XRXR Y FertilisationXRXR Y XRXR XRXRXRXR XRYXRY XrXr XRXrXRXr XrYXrY © 2007 Paul Billiet ODWSODWS

F2F2 PhenotypesFemalesMales Red- eyed White- eyed Red- eyed White- eyed ExpectedAllNone50% Observed This gene has its LOCUS on the X-chromosome It is said to be SEX-LINKED © 2007 Paul Billiet ODWSODWS

X-linked genes In sex linked characteristics the reciprocal crosses do not give the same results For X-linked genes fathers do not pass the mutant allele onto their sons For X-linked genes fathers pass the mutant allele onto their daughters who are carriers Carrier mothers may pass the allele onto their sons (50% chance) Females showing the trait for an X-linked mutant allele can exist but they are rare Female carriers may show patches of cells with either trait due to X chromosome inactivation © 2007 Paul Billiet ODWSODWS

Tortioseshell Cats are Female © 2007 Paul Billiet ODWSODWS

Daltonism = Red-Green Colourblindness Normal vision Colour blind simulation © 2007 Paul Billiet ODWSODWS

LIGHTLIGHT Optic nerve fibres Ganglion layer Bipolar cells (neurones) Synapse layer Nuclear layer Inner segments packed with mitochondria Rod and cone outer segments Rod cell Cone cell The retina © 2007 Paul Billiet ODWSODWS

PHOTORECEPTION VISIONCOLOURMONOCHROME PHOTORECEPTORCONES: red sensitive 560nm green sensitive 530nm blue sensitive 420nm RODS: max. sensitivity 505nm DISTRIBUTIONConcentrated in the foveaWidely spread over whole retina, absent from fovea PIGMENTS3 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 BLEACHINGSlowFast (very sensitive) REGENERATIONSlow (after images in bright light, complementary colours) Fast USEDaylight vision Light adaptation 5 min Night vision Dark adaptation 20 min or wear red goggles! © 2007 Paul Billiet ODWSODWS

Blood Clotting and Haemophilia A simplified scheme of the important steps Damaged blood vessels Prothrombin Inactive enzyme Thrombin Active enzyme Fibrinogen Globular protein Fibrin = Clot Fibrous protein © 2007 Paul Billiet ODWSODWS

Contact with collagen fibres in blood vessels Factor XII (inactive)  Factor XII (active) Factor XI (inactive)  Factor XI (active) Factor IX (inactive)  Factor IX (active) Antihaemophilic factor B Factor X (inactive)  Factor X (active) Factor II (inactive)  Factor II (active) ProthrombinThrombin Factor I (inactive)  Factor I (active) FibrinogenFibrin Factor III Thromboplastin released from blood vessel walls Factor VIII Antihaemophilic factor A Ca 2+ ions and blood platelets Vitamin K precursor © 2007 Paul Billiet ODWSODWS

The antihaemophilic factors The blood clotting reaction is an enzyme cascade involving Factors XII, XI, IX, X and II Each of these enzymes are proteases that cut the next protein in line Other factors including proteins like Factor VIII are essential as coenzymes © 2007 Paul Billiet ODWSODWS

Heamophilia About 85% of haemophiliacs suffer from classic haemophilia (1 male in ) They cannot produce factor VIII The rest show Christmas disease where they cannot make factor IX The genes for both forms of haemophilia are sex linked Haemophiliacs do clot their blood slowly because there is an alternative pathway via thromboplastin © 2007 Paul Billiet ODWSODWS