Transmission Genetics

1
Transmission Genetics

• Chapters 14-15 in the textbook
• Focus on Section 14.4-human traits

2
Disambiguation

• Historically, heredity regarded as a blending
  process of parental traits
• Heredity first studied scientifically in 1860s
• Experimental organism-garden pea
• Blending does not really occur
• Fruit fly studies extend knowledge

3
Transmission Genetics-some definitions

• Genotype-genetic composition of an organism for
  trait under study
• Phenotype-appearance of organism for trait under
  study
• Allele-variant form of a gene

4
Transmission Genetics-some definitions

• Homozygous-two copies of same allele
• Heterozygous-different alleles
• Dominant-allele that is expressed at the
  phenotypic level being examined
• Recessive-allele that is not expressed at the
  phenotypic level being examined

5
Transmission Genetics- a medical example

• Blood transfusion-a haphazard process
• Many fatalities in early trials
• Systematic basis in early 20th century
• Landsteiner and others
• Genetic basis understood by 1920s
• Case studies and family histories

6
Transmission Genetics-ABO blood groups

• ABO blood groups based on cell surface
  glycoproteins
• Type A blood has Type A sugars
• Type O has neither A nor B

7
Transmission Genetics-ABO blood group biochemistry

• CHO chain named H substance attached to lipid
  named sphingosine
• Blood group A-GalNAc attached to H
• Blood group B-Gal attached to H
• Enzyme is ABO blood group transferase
• ER to plasma membrane

8
Transmission Genetics-ABO blood group genomics
Genomic context chromosome 9 Location
9q34.1-q34.2 One gene, or locus, aka I or
I locus Many variant forms (alleles)
exist Subtle variations in blood cell surface
properties
9
Transmission Genetics-ABO blood group genetics

• With this background-a hypothetical case
• Population of true-breeding A individuals
• (type A phenotype)
• Second population of true-breeding O individuals
  (type O phenotype)
• Genetic outcomes if A marries O?

10
Transmission Genetics-ABO blood group genetics

• What is the genotype for true-breeding A?
• What is the genotype for true-breeding O?

11
Transmission Genetics-ABO blood group genetics

• Reproduction of A x O involves meiosis and
  fertilization (sexual reproduction)
• What are the gamete genotypes for true-breeding
  A?
• What are the gamete genotypes for true-breeding O?

12
Transmission Genetics-ABO blood group genetics
13
Transmission Genetics-ABO blood group genetics

• IA IO individuals are heterozygous
• What cell surface CHOs are present?
• What is the phenotype of an IA IO heterozygote?
• Which allele is the dominant allele?
• Recessive allele-lower case, therefore IO is i
• Heterozygote is IAi
• What happens when IAi x IAi?

14
Transmission Genetics-ABO blood group genetics

• Types AB and O always correlate with one genotype
• Types A and B may be homozygous or heterozygous
• Antibodies made against non-self

15
Transmission Genetics-ABO blood group genetics

• IA , IB and i are three alleles of the same gene
• A multiple allele system
• Very common in humans due to the many variant
  forms that exist for all genes
• CFTR gene-exists in over 1000 forms
• In homozygous state causes cystic fibrosis but
  symptoms may vary depending upon alleles
  inherited

16
Transmission Genetics-ABO blood group genetics

• IA gt i, IB gt I
• But IA IB
• IA and IB are codominant
• How many genotypes/phenotypes can exist with a
  multiple allele series with 3 alleles such as
  above?

17
Transmission Genetics-quantitative inheritance

• Phenotypic trait controlled by more than one gene
• Each gene may have many alleles
• Dominance relationships may be complex
• This is the usual situation for most human traits
• Human hair color controlled by at least two gene
  pairs brown gt blond and not-red gt red
• quantitative inheritance or polygenic
  inheritance

18
Transmission Genetics-quantitative inheritance

• Model for skin color inheritance with three
  alleles
• Bell curve or normal distribution

19
Transmission Genetics-penetrance

• The proportion or of individuals carrying a
  gene who show expression of the gene
• For unknown reasons-genes may be present but not
  expressed at the phenotypic level.

20
Transmission Genetics-penetrance in Huntingtons
Disease

• Neurodegenerative disorder
• Caused by dominant gene at 4p16.3
• Penetrance is incomplete-95
• Penentrance is delayed until late adulthood

21
Transmission Genetics-Huntingtons Disease
22
Transmission Genetics-Tay-Sachs

• Lysosomal storage disorder due to hexoseaminidase
  A deficiency
• Ganglioside lipid accumulates
• Disease gene frequent (3?) in Ashkenazi
  populations
• Penetrance delayed usually

23
Transmission Genetics-Tay-Sachs

• Recessive gene HEXA
• Cytogenetic Location 15q23-q24, base pairs
  70,422,832 to 70,455,392
• 25 chance of disease in children of carriers
• Why is the gene present at high frequencies in
  some populations?
• Heterozygote advantage? (selection)
• or
• Accidental?
• (founder effect)