MBG 2040 Lecture Notes - Lecture 2: Transferase, Blood Type, Antigen
2 May 2018
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Extensions of Mendelism
Chapter 4
Outline:
• Allelic variation and gene function
• Gene action: from genotype to phenotype
• Inbreeding
Complete dominance and complete recessiveness are the extremes of a range
• Mendel came to the conclusion that genetic factors are inherited independently
o *note: with non-medelian genetics, the genes are inherited independently still but the traits
and phenotypes are more complete
• Complete dominance:
o The dominant allele will always eclipse the trait of the recessive one
o BB = Bb NOT bb
• Incomplete dominance:
o BB, Bb and bb all differ phenotypically
o Bb is the intermediate between BB and bb
o Ex. Flower colour (red, white, pink)
• Red = WW (2x amount of gene product)
• Pink = Ww (x amount of gene product)
▪ *one copy means 1/2 enzyme --> pink
• White = ww (0 amount of gene product)
▪ *codes non-functional enzyme
o Distribution - 1:2:1
• Co-dominance:
o Bb is phenotypically different from BB and bb
o Ex. Blood type
• Gene I encodes transferase enzyme
• Three alleles: IA, IB, i
• Blood types:
▪ A: IA encodes a transferase which adds acetyl-galactosamine to a surface antigen
(--> A-type blood antigen)
• IAIA OR IAi
▪ B: IB encodes a transferase which adds galactose (-->B-type antigen)
• IBIB OR IBi
▪ O: i encodes a non-functional transferase
• ii
▪ AB: IA and IB encode 2 different transferase together (--> AB-type antigen)
• IAIB
Multiple Alleles and Dominance:
• Ex. Coat colour in Rabbits
o Albino (cc) - white colour
• c=complete loss of function allele
o Himalayan (chch) - black hairs on extremities (white everywhere else)
• h=significant loss of function allele
o Chinchilla (cchcch) - white hair with black tips
• ch=moderate loss of function allele
o Wild-type (c+c+) - coloured hair
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• c+=full function allele
• Genes have many alleles
o Some of these alleles are common, others are rare
o Frequency of a particular allele varies from population to population
o Different alleles have different levels of functionality
• Can be produced by point mutations at locus
o Population: multiple alleles may exist
o Individual (diploid): only two alleles coexist in each cell
• Ex. Coat colour in Cats
o Alleles:
• C = full colour
• cb = burmese
• cs = siamese
• c = white, blue eyes
• ca = albino, pink eyes
o C > cb = cs > c > ca
• This represents a dominance series or allelic series
• Describes the dominance hierarchy of multiple alleles
▪ A null allele is non-functional
▪ A hypomorphic allele has partial function
• To identify gene mutation, assay = allelsim test
• Testing gene mutations for allelism:
o Allelism means that two similar phenotypes are caused by different mutations of the same
gene
o If the phenotype is caused by mutations in two different genes, we say that mutations are non-
allelic
o The test for allelism is called "complementation) - if the mutations are not in the same gene,
the dihybrid cross between two mutants will produce a wild type phenotype
• Ex. Test if two identical homozygous phenotypes (white fur) a and a* are caused by mutations in
the same gene or not
o You perform a dihybrid test with homozygous aaXX and XXa*a* individuals
• Note: XX is an unknown gene
o Possible outcomes:
• aXa*X --> wild-type phenotype (a and a* are not allelic)
• aa*XX --> mutant phenotype (a and a* are allelic)
• Explanation of allelism with the C gene series (rabbit example)
o Cross: cchcch X chch
o If progeny is wild-type, the two mutations are in different genes (non-allelic mutations)
o If progeny is a light chincilla with black tips, the two mutations are on the same gene (allelic
mutations)
o *alleles are co-dominant
Effects of mutations:
• Visible
• Lethal
• Dominant
• Recessive
• Loss-of-function
• Gain-of-function
Terminology:
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• Wild-type allele - a functional enzyme or other protein is produced
• Visible mutations - affect morphology of an organ or tissue
• Sterile mutations - produce sterile progeny
• Lethal mutations - cause death in homozygous or heterozygous organisms
• Loss-of-function mutations - mutant allele produces an enzyme or other protein is no longer being
produced/produced at lower levels/is non-functional
• Gain-of-function mutations - mutant allele produces a protein that has increased (detrimental)
function
Ex. Huntington's Disease
• HD is a dominant gain-of-function allele, in which the mutant allele produces a protein that has new
detrimental activity
• In many cases, the mutant protein interferes with the activity of the wild-type allele = dominant-
negative mutation
Ex. Tailless Cats (Manx)
• Manx is a dominant loss-of-function allele
• In the heterozygote, half as much protein is synthesized and this is not sufficient for a normal
phenotype = haplo-insufficient allele
o mm = normal tail
o Mm = no tail
o MM = lethal
Mutations in essential genes lead to a lethal phenotype
• AY/A+ X AY/A+ (both yellow) gives a phenotypic ration 2:1 (yellow:brown)
o The AY allele is a recessive lethal allele --> causes death only in recessive homozygotes
• The effect of the allele on colour is dominant
o Note: A+A+ = wild-type (brown)
• The agouty gene regulates the pigementation of the fur
o Since AY/A+ rats have a yellow coat, the AY is a dominant allele
Mechanistic Explanation of Different Phenotypes
• Genes produce polypeptides
• Mutations affect genes (DNA)
• These mutations cause changes in the activity of these polypeptides
• These changes in the activity of the polypeptide are reflected in the phenotype
• Mutations:
o Recessive amorphic loss-of-function allele does not produce a functional polypeptide -->
severe mutant phenotype
o Recessive hypomorphic loss-of-function allele produces a partially functional polypeptide -->
mild mutant phenotype
o Dominant-negative allele produce a polypeptide that interferes with the wild-type polypeptide
--> severe mutant phenotype
Key Points:
• Genes often have multiple alleles
• Mutant alleles may be dominant, recessive, incompletely dominant, or codominant
• If a hybrid that inherited a recessive mutation from each of its parents has a mutant phenotype, then
the recessive mutations are alleles of the same gene
o If the hybrid has a wild phenotype, the recessive mutations are alleles of different genes
(complementation and allelism)
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Document Summary
Outline: allelic variation and gene function, gene action: from genotype to phenotype. Incomplete dominance: bb, bb and bb all differ phenotypically, bb is the intermediate between bb and bb, ex. Blood type: gene i encodes transferase enzyme, three alleles: ia, ib, i, blood types, a: ia encodes a transferase which adds acetyl-galactosamine to a surface antigen (--> a-type blood antigen) Iaia or iai: b: ib encodes a transferase which adds galactose (-->b-type antigen) Ibib or ibi: o: i encodes a non-functional transferase ii, ab: ia and ib encode 2 different transferase together (--> ab-type antigen) Individual (diploid): only two alleles coexist in each cell: ex. If progeny is wild-type, the two mutations are in different genes (non-allelic mutations) If progeny is a light chincilla with black tips, the two mutations are on the same gene (allelic mutations: *alleles are co-dominant. Effects of mutations: visible, lethal, dominant, recessive, loss-of-function, gain-of-function.
