Genetic Disease Flashcards
Mutations that affect germ cells can be transmitted to progeny?
-true
What are somatic mutations/
-these mutations can result in tumors or developmental malformations
What is a trinucleotide repeat mutation?
-amplification of sequence of 3 nucleotides
What is a single nucleotide polymorphism?
- variation in just one nucleotide at a single site on DNA molecule
- may be markers for multigenic complex diseases such as diabetes or hypertension
What are copy number variations?
- different numbers of large contiguous stretches of DNA, many base pairs.
- 1/2 involve gene-coding sequences (may account for phenotypic variation)
What are epigenetic changes?
- modulation of gene expression without altered DNA sequence
- important in development as well as normal homeostasis
What is the effect of methylation on protein synthesis?
- methylation of promoter regions makes them inaccessible to RNA polymerase
- reduces protein synthesis
What are miRNA’s?
-miRNA’s inhibit translation of their target messenger RNAs into their corresponding enzymes
What is reduced or incomplete penetrance?
-person with mutant gene but doesn’t or only partially expresses it phenotypically
What is variable expressivity?
-trait seen phenotypically in all individuals having mutant gene but expressed differently among individuals
What is a de novo mutation?
-affected individuals may not have affected parents because their disease arose from a new mutation
What is neurofibromatosis an example of?
- variable expressivity
- AD disease with nearly 100% penetrance
- nearly everyone with this mutation will show evidence of this relative common condition
- highly variable expressivity
For autosomal recessive disorders, if the mutant gene is rare, there is a strong probability that the affected child is the product of what kind of relationship?
-consanguinous
What are the main characteristics of autosomal recessive disorders?
- many present with enzyme defect that produce inborn errors of metabolism
- carriers may possess reduced amounts of normal enzyme
- age of onset is early in life
- expression tends to be uniform and complete penetrance is common
To date, all sex-linked disorders are carried on which chromosome?
-X chromosome
What are the characteristics of X-linked disorders?
- almost all recessive
- women need 2 copies to be affected
- all men who inherit mutation are affected
- heterozygous females are carriers
What are the characteristics of lyonization?
- 16 days after conception, 1 X chromosome is randomly inactivated in all cells within zygote
- inactivated X remain inactivated in progeny
- typically females are an even mixture of normal and abnormal chromosomes
What is unfavorable lyonization?
-inactivation of an abnormally high percentage of normal X chromosomes, leading to clinical evidence of a recessive disease in a heterozygous female
What is the one x-linked dominant that was mentioned?
-Oral-facial digital syndrome type I
What are the characteristics of Marfan syndrome?
- AD disorder of CT due to mutation of FBN1 gene
- results in abnormal fibrilin 1:5000
- tall, thin body with abnormally long legs, arms and finbers
- dislocation of lens of eye, aortic aneurysm/Abe Lincoln, sudden death of bball players
What are the characteristics of Ehlers-Danlos Syndromes?
- 6 different types exist
- problem of collagen synthesis
- hypertensible skin and hypermobile joints
- skin fragility and delayed wound healing
- rupture of colon, large arteries
- hernias
What are the characteristics of familial hypercholesterolemia?
- 1:500 in pop
- mutation in gene for LDL receptor
- results in impaired metabolism and increased LDL cholesterol in plasma
- xanthomas and premature atherosclerosis
- homozygotes die of MI before age 20
- treat with clot buster- Iomitapide (very strong med)
What are the characteristics of phenylketonuria?
- AR disorder 1:10000 caucasian infants
- lack of phenylalanine hydroxylase–> hyperphenylalaninemia and PKU
- Affected infants normal at birth–> elevated phenylalanine levels impair brain development and mental retardation evident by 6 mo of age
- screening of newborns mandatory in U.S.
- restriction of dietary phenylalanine will prevent metal retardation
What are the characteristics of lysosomal storage diseases?
- AR transmission
- commonly affect infants and young children
- accumulation of large molecules in macrophages with hepatosplenomegaly
- frequent CNS involvement, mental retardation/early death
