Mendelian Inheritance I Flashcards
what is the “locus”?
position of a gene on a chromosome
what are “alleles”?
different forms of a gene that can occupy a single locus
what is the “wild type”?
m/c form
what is a “mutation”?
form that differs from wild type, can be normal variation or disease causing
what is “polymorphism”?
2 or more alleles for a given locus, each present is a populate at a frequency of at least greater than 1%
what is “genotype”?
alleles present at a given locus
what is “phenotype”?
observable expression of a genotype as a morphological, biochemical or cellular trait
what is a compound heterozygote?
genotype with 2 different mutant alleles at the same locus, they are both different and both defective
what are the mendelian principles? (3)
principle of dominance
principle of segregation
principle of independent assortment
what is the principle of dominance?
genes come in pairs, one copy from each parent
individual genes have different alleles, some are expressed over others
what is the principle of segregation?
organisms inherit 2 alleles for each trait and during gamete formation, the pairs separate thus that each gamete has a single allele for every trait
this allows for the ability of a single trait to be traced through generations
what is the principle of independent assortment?
genes located at different loci are transmitted independently
allele pairs are randomly reunited at fertilization
an allele at one locus has no effect on an allele at a different locus
explain “dominance”
a property of the relationship between a pair of alleles- considered dominant if expressed in heterozygote (only one copy required for expression)
what are the characteristics of autosomal dominant inheritance? (5)
phenotype present in every generation vertical transmission (each affected offspring with an affected parent) offspring of affected parent has 50% chance of inheriting phenotypically normal parents usually do not transmit male-to-male transmission can occur
in AD disorders, will unaffected parents have affected offspring?
no
what is incomplete dominance?
intermediate phenotype exists between 2 alleles
AB is an intermediate between AB and BB
what is an example of a condition with incomplete dominance?
achondroplasia
what are the 3 allelic possibilities for achondroplasia?
dd- normal
Dd- achondroplasia
DD- lethal severe achondroplasia
what is codominanace?
phenotype has features of both alleles
what is an example of codominance?
ABO blood typing
A+B are codominant, O is recessive
what is a “de novo” mutation?
child born with a genetic d/o when there is no family hx of the disease due to spontaneous mutation at the time of conception
recurrence risk - for the parents to have another child with the same- less than 1%, for the affected offspring to have a child with the same- 50%
what is achondroplasia type II?
rare skeletal d/o characterized by mutation in collagen II, autosomal dominant, typically from de novo mutation bc survival past puberty is rare
what is germ line mosaicism?
presence of more than one genetically distinct cell line in the germ cells of one of the parents, cannot test for
when in germ line mosaicism suspected?
when there are 2 or more children with an autosomal dominant d/o and no family hx- like hemophilia A, DMD, OI
what is somatic mosaicism?
presence of more than 1 somatic cell line in individuals
what is tissue mosaicism?
occurs after conception, confined to one part of the body
what are some AD disorders that present in adulthood?
huntington’s disease and breast CA
what are the implications of AD d/o that present later in life?
may present after patient has had children
what is penetrance? what are the 2 senarios?
the probability that a gene will be expressed
1- all or nothing
2- reduces/variable- hard to determine
what are some examples of diseases with variable penetrance?
HNPCC- 80%
split-hand deformity- 70%
unable to determine who will be affected phenotypically
what is variable expression?
differing severity of disease among people with the same genotype, exhibits great variability
what is pleiotropy?
one gene that produces multiple different effects
what is locus heterogeneity?
single d/o that is caused by mutations in genes at different loci, ex- hereditary breast CA (BRCA1/2)
what is allelic heterogeneity?
a single disorder caused by different mutations in the same gene (like CF)
what is phenotypic heterogeneity?
different mutations in the same gene give rise to different phenotypes
what is an example of phenotypic heterogeneity?
craniosynostosis syndromes- FGFR2 gene
Pfieffer synd-
Apert synd- dev delay
Crouzon synd-
characteristics of autosomal recessive inheritance
clinical manifestations only in homozygous for mutant
not typically in every generation
equal male/female affectedness
risk is 1/4 for each pregnancy when both parents carriers
what is consanguinity?
parents share a common ancestor
what increases risk for AR disorders?
parents both from the same ethnic group
what is heterozygote advantage?
persistence of a carrier state bc it provides survival advantage
