Genetics-SIngle Gene Disorders Flashcards
What are the different types of single gene disorders?
Autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive
What pedigree characteristic is often a giveaway for autosomal recessive disorders?
Consanguinity
Who are the obligate heterozygotes if this is an autosomal recessive disorder?
They must be carriers 1) Because the parents made affected progeny and 2) Affected progeny must have at least carrier progeny.
Single gene homozygous mutations are rare, what mutations most often cause autosomal recessive disorders?
Compound heterozygotes. This happens when there are different mutations that are within the same mutated gene that still cause disease.
What is the typical target of autosomal recessive diseases?
Enzyme defects (at least 50% enzyme deficiency)
Mutation in familial hypercholesterolemia?
Autosomal dominant haploinsufficiency: the normal protein LDL-R is insufficient and people die early from atherosclerotic disease.
Mutation in osteogenesis imperfecta?
Autosomal dominant negative effect: the mutant protein interferes with the function of the normal protein. In type I only the alpha-1 collagen protein is affected and symptoms are milder. In type II 3/4 collagen chains are affected and babies die in utero.
Mutation in achondroplasia or Huntington disease?
Autosomal dominant gain of function: achondroplasia has an overactive FGFR3 receptor, Huntington disease has a cytotoxic mutant protein.
What type of inheritance pattern is this?
X-linked recessive. All daughter of affected male are carriers and carrier females will have 50% affected sons. Affected females have affected fathers and mothers.
What type of inheritance pattern is this?
X-linked dominant. Females are affect 2x more often than men. Men transmit the gene to all daughters.
What X-linked diseases affect both males and females?
X-linked dominant fragile X syndrome and vitamin D resistant rickets.
What X-linked diseases are lethal in males?
Aicardi syndrome, incontinentia pigmenti and Rett syndrome
Vertical transmission
Typically dominant transmission. Horizontal transmission is typically recessive.
Father transmits disease to son
Must be autosomal.
Type of inheritance pattern that could also be autosomal dominant even if there is no male to male transmission, males transmit the disease to their daughters and more women are affected than men.
X-linked dominant
How does genetic heterogeneity contribute to disease presentation?
The same condition is caused by mutations in different genes.
Why doesn’t III:1 have the disease?
They do, it just has incomplete penetrance in that individual (likelihood mutation will result in disease)
What type of disease would give you two children with dominant disease in a family without any prior history?
Germline (gonadal) mosaicism. This is caused by a mutation the germ stem cell so you have some affected gametes and some unaffected gametes on fertilization.
Expressivity
Degree of manifestation of the same mutant allele in different people
