Mendelian Genetics/single Gene Inheritance

Front 1

Define the following:
1. Locus
2. Allele
3. Homozygote
4. Heterozygote
5. Hemizygote
6. Genotype
7. Phenotype

Back 1

1. Position of gene on chromosome
2. Alternative forms of a gene found at the same locus on homologous chromosome
3. Identical alleles at a locus
4. 2 different alleles at a locus
5. Only 1 allele at a locus. Usually in X-linked trait in males
6. Genetic constitution of a gene
7. Observable traits

Front 2

Define the following and give ex. where applicable:
1. Genetic heterogeneity
2. Variable expression
3. Pleiotropy
4. Reduced/Incomplete penetrance
5. Consanguinity
6. Pedigree
7. Proband
8. Sibship

Back 2

1. Phenomenon where same phenotype is caused by different genotypic abnormalities. ex. osteogenesis imperfecta
2. Same genotype showing as different phenotypes in diff indvs. Ex. Neurofibroma
3. Mutant genes affecting different organ systems. ex. Marfan's
4. Reduced number in popn of ppl carrying genotype AND showing phenotype
5. Relationship btw couples who are blood relatives
6. Short-hand method of communicating genetic familial relationships and understanding patterns of single gene inheritance
7. Indv thru whom genetic disorder is first ascertained. Reference person in a pedigree
8. Relationship among siblings

Front 3

Difference btw genetic heterogeneity and pleiotropy

Back 3

Genetic heterogeneity: Can say opp to variable expression, in that, 1 phenotype is caused by diff genetic mutations
Ex: Osteogenesis imperfecta caused by different mutations

Pleiotropy: A diff concept with an emphasis on the fact that multiple organ sys in an indv are affected by a single abnormal gene
Ex. Marfan's causes cardiac, ocular and skeletal probs

Front 4

What is allelic heterogeneity vs. Locus/nonallelic heterogeneity

Back 4

When the abnormal phenotype is caused by different mutations in the same locus ex. CFTR where hundreds of mutations have been described for the CF phenotype
VS.
Where mutations occur at 2 or more separate loci. Ex. congenital sensorineural deafness in which dominant, recessive and x-linked forms have all been described

Front 5

Definition of penetrance

Back 5

= # of ppl with genotype showing phenotype / total # of ppl with genotype

Front 6

What are the pedigree symbols for:
Unaffected male, affected female, deceased, mating, consanguinous mating, sex unspecified, heterozygous for autosomal recessive trait, heterozygous for x-linked recessive trait, dizygotic twins, monozygotic twins, spontaneous abortions (miscarriage), stillbirth, pregnancy

Back 6

Front 7

What are the inheritance patterns?

Back 7

Autosomal dominant, autosomal recessive, x-linked recessive and dominant

Front 8

What are distinguishing features of autosomal dominant trait patterns?

Back 8

1. male --> male transmission
2. disorder doesn't skip generations
3. phenotypically normal don't transmit to chd
4. chd of affected parents, have 50% chance of inheriting
5. males and females have equal chances of inheriting

Front 9

What are distinguishing features of autosomal recessive trait patterns?

Back 9

1. Disorder skips some generations; appears in sibships of proband
2. Parents are assymptomatic
3. In calculating risk of inheriting, sibs who don't have disease have 2/3 chance of being carriers, and for unborn chd, there is a 1/4 chance of getting disorder

Front 10

What are distinguishing features of x-linked dominant trait patterns?

Back 10

1. Affected Dad? All daughters will show it! No son will have it
2. Carrier Mom? 50% of both male and female chd to show it

****In drawing punnet square, remember that dominant phenotype is bad so capital letters will transmit disease and small letters will NOT transmit disease

Front 11

What are distinguishing features of x-ljnked recessive trait patterns?

Back 11

1. Affected Dad? All daughters will carry it; no son will have it
2. Carrier Mom? 50% of sons will show it; 50% of daughters will carry it
3. Incidence higher in males

Front 12

What is the Lyon hypothesis?

Back 12

Refers to the concept of x-inactivation and its resulting gene expression.

Principles:
In female SOMATIC cells, only one X is active, the second x is condensed as a Barr body in interphase cells
This happens in early embryonic event
This inactive X can be paternal or maternal X

Front 13

Why is there variable expressivity in x-linked disorders?

Back 13

This results from the fact that the inactive X can be paternal or maternal X and is distributed randomly. So most females are expected to have half their cells with the maternal x and the other half with the paternal x. But some deviate from this proportion. So, let's say, the paternal X has the mutation, if more than half of the affected female's cells if from her Dad then she'll show higher degree of the disorder.

Front 14

What is dosage compensation in terms of x-linked genes?

Back 14

This refers to the fact that females express only one allele of their x-linked genes although they actually have two alleles.

Front 15

What inheritance pattern does hemophilia A or factor VIII exhibit?

Back 15

X-linked recessive

Front 16

How is fitness of a condition in a popn measured?

What does a fitness of 0 or 1 mean.

Back 16

It is measured by the number of affected persons who are able to survive to reproductive age and to have offspring.

A fitness of 0 means no offspring has survived so all cases represent new mutations; with a fitness of 1, new mutations are rare.

Ex. huntington's disease has a fitness of 1 while thanatotropic dysplasia (skeletal dysplasia) has a fitness of 0 and is invariable lethal in the newborn

Front 17

Example of disease concentrated in genetic isolates

Back 17

Tay Sach's disease carrier rate in the Ashkenazi Jews is 1/30

Tay-Sachs disease is a deadly disease of the nervous system passed down through families

Front 18

What inheritance pattern is exhibited by Duchenne muscular dystrophy?

Back 18

X-linked recessive

Front 19

What inheritance pattern is exhibited by Marfan's?

Back 19

Autosomal dominant

Front 20

What inheritance pattern is exhibited by Marfan's?

Back 20

Mostly autosomal dominant but some exhibit autosomal recessive trait pattern

Front 21

How is reduced penetrance exhibited?
What are some examples of reduced penetrance?

Back 21

Reduced penetrance exhibits autosomal dominant trait patterns but with fewer indvs.

Ex. Polycystic kidney disease is an age-dependent penetrance

Front 22

What inheritance pattern is exhibited by Alkaptonuria?

Back 22

Autosomal recessive.

Alkaptonuria is a rare condition in which a person's urine turns a dark brownish-black color when exposed to air. The gene defect makes the body unable to properly break down certain amino acids (tyrosine and phenylalanine).