HCR 240: Genetic Diseases - Inheritable Alleles

What is an allel

different forms of a gene, typically inherit one from mother and one from father

What does homozygous and heterozygous mean

- homozygous: alleles that are identical (AA or aa)
- heterozygous means alleles that are different (Aa)

What does dominant, recessive, and co-dominant mean

- dominant: allele with observable effect (denoted by capital letter)
- recessive: allele with non-observable effect in the presence of a dominant allele (denoted by lowercase letter)
- co-dominant: both alleles have an observable affect (ex: blood type AB)

What is genotype vs phenotype

- genotype: composition of genes at a given locus (dna → your genes)
- phenotype: outward appearance of an individual (genotype + environment)

What is a carrier in genetics

individual with disease-causing allele but with a normal phenotype. Most typically occurs with heterozygous alleles
(carries disease but do not have it)

How do you determine the sex of a child with genetics

one copy of the Y chromosome is sufficient to initiate the process of gonadal differentiation that produces a male fetus → number of X chromosomes does not alter this process.

what is the sex-determining region on the Y chromosome called

SRY

What are 4 major types of genetic disease inheritance and which ones are sex linked

- autosomal dominance and autosomal recessive are NOT sex linked (autosomal means not sex related)
- X-linked dominant and X-linked recessive ARE sex linked

What is autosomal dominant

diseases are rare and condition is expressed equally in males and females (not sex linked) → transmission of affected individuals to their offsprings is not sex-linked

Describe transmission in relation to autosomal dominant

- there is no generational skipping → all affected children will hav an affected parent, nonaffected parents cannot pass it to their children, exceptions may occur is there is a germline mosaicism
- transmission is ~50%
- ex: huntington’s disease

What is a germline mosaicism

parent carries the mutation in his or her gamete cells but does not have the autosomal dominant disease in his or her somatic cells (parent with normal phenotype; asymptomatic carrier)
- disease can pass on to children despite no recorded family history

What is genetic penetrance

percentage of individuals who have the diseased genotype and express the diseases phenotype

What is gene expressivity

extent of variation in a phenotype associated with a particular genotype (how much of the disease are you expressing)
- can be caused by modifier genes, environmental factors, and mutations

Describe neurofibromatosis type 1

autosomal dominant, expressivity varies from brown spots on skin to malignant tumors, scoliosis, gliomas, and neuromas

What number chromosomes are autosomal

1-22 because the 23 chromosome is sex related

What is autosomal recessive

- rare to have the disease, more common to be carrier
- condition is expressed equally in males and females (not sex linked)
- transmission of affected individuals to their offsprings is not sex-linked

What must you be to be autosomal recessive

since the abnormal allele is recessive, the person must be homozygous to express the disease (dd) → this means that both parents must be carriers (dd or Dd)
- most commonly, both parents are heterozygous (Dd)
*you need 2 copies of the disease to have the disease → if either parent is homozygous for normal gene, no children will be affected but can be carriers

What is the percentage of heterozygous carriers passing on the disease

- 25% chance of passing on the disease to their children
- 25% chance of not passing the disease
- 50% chance of having children who are also carriers
*generational skips can occur with autosomal recessive diseases

What is a type of hereditary disorder associated with autosomal recessive

cystic fibrosis → mutated gene forms defective chloride channels, which leads to a salt imbalance that result in abnormally thick, dehydrated mucus
- affects lungs and pancreas
- patients typically do not survive pass 61 years old

What is consanguinity

- an autosomal recessive genetic relationship that involve the mating of 2 related individual (inbreeding).
- proportion of shared genes depends on closeness of biologic relationship
- dramatically increases recurrence risk of recessive disorders

What is X-linked dominant

- X-linked dominant disorders are incredibly rare
- females are more likely to be affected by X-linked dominant disorders than males
- ex of X-linked dominant disorder: fragile X syndrome

Describe X-linked dominant pass down percentage of males vs females to their children

- males with X-linked disorder have 100% chance of passing the disorder to daughters and 0% chance of passing it to sons
- females with X-linked disorders have 50% chance of passing it to their sons or daughters

What is X-linked recessive

since males only have 1 copy of the X chromosome, they are significantly more likely to be affected by x-linked recessive disorders → males only need 1 copy of the recessive gene whereas females would need 2

Describe the pass down of an affected father in X-linked recessive

an affected father will:
- never be able to pass the gene to his sons (can only give Y chromosomes)
- always pass the gene to his daughters (must give affected X chromosome) who will then become carriers
*generational skips may occur due to female carriers

What is an example of an X-linked recessive disease

Duchenne Muscular Dystrophy → occurs 1 in 3500 males vs 1 in 50,000,000 females
- exhibits progressive muscular degeneration
- deletion of DMD gene causes dystrophin to not work properly; consequently, muscle cells do not survive
(disease: does not make dystrophin, so the more you move, the more you lose muscle)

What are Barr Bodies

even though females have 2 X chromosomes, they only need 1 set of X chromosomes proteins → to correct for this, each cell will select 1 X chromosome to deactivate → the deactivated chromosome becomes a barr body (15% of genes on barr body may escape deactivation)