Transmission Genetics

Chapters 14-15 in the textbook

Focus on Section 14.4-human traits

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

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

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

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

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

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

Transmission Genetics-ABO blood group genomics

Genomic contextchromosome: 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

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?

Transmission Genetics-ABO blood group genetics

• What is the genotype for true-breeding A?

• What is the genotype for true-breeding O?

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?

Transmission Genetics-ABO blood group genetics

Mom’s gametes

Dad’s gametes

IO IO

IA

IA

Transmission Genetics-ABO blood group genetics

• IA IO individuals are heterozygous

• What cell surface CHO’s 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?

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

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

Transmission Genetics-ABO blood group genetics

• IA > i, IB > 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?

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 > blond and not-red > red• “quantitative inheritance” or “polygenic

inheritance”

Transmission Genetics-quantitative inheritance

• Model for skin color inheritance with three alleles

• Bell curve or normal distribution

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.

Transmission Genetics-penetrance in Huntington’s Disease

• Neurodegenerative disorder

• Caused by dominant gene at 4p16.3

• Penetrance is incomplete-95%

• Penentrance is delayed until late adulthood

Transmission Genetics-Huntington’s Disease

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

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)

orAccidental? (founder effect)