CBCL1: Mendelian Inheritance and Chromosomal Disorders Flashcards
incomplete penetrance
patient has the mutation but no disease
non-penetrance
no phenotype because of modifying factors/non-genetic mechanisms, but the genetic mutation is present
GOF
produce either an increased amount or increased activity of the product aka protein…enhanced activity of its existing function or a new function
ex: Huntington’s Disease -> CAG triplet expansions
LOF
produce either a reduced amount or a reduced activity of the product
typically have a minimal effect on the phenotype unless both alleles are affected
dominant negative
an effect that results from LOF…inherited in a dominant fashion
normal function of the product is lost AND the abnormal product interferes with the product of the normal allele
ie these are alleles that produce a non-functional protein that can still interact with other members of a complex, thereby inactivating a whole complex
typically cause a more severe phenotype than does the complete absence of the product
recessive negative
abnormal protein that is inherited in a negative fashion (most mutant alleles)
what causes somatic mosaicism?
two different tissues having different karyotypes -> suggests an error during mitosis in the early embryo
obligate carrier
an individual who is a carrier of a mutation but does not have the phenotype
characteristic of non-penetrant disorders
variable expressivity
range of signs and symptoms occurring in different people with the same genetic condition
“difference in symptoms”
characteristic of non-penetrant disorders
locus heterogeneity
mutation in different genes may explain one variant phenotype
allelic heterogeneity
different alleles in the same gene can cause a similar variant phenotype
anticipation
occurs when symptoms of a genetic disorder appear at an earlier onset with each generation
common with trinucleotide repeat disease sine the repeat can expand during meiosis and increase with each successive generation
haplotype
a set of polymorphisms in different genes that reside closely on a given chromosome and are often inherited together
can correlate with disease severity
null allele
no product or function results from the allele
when to use whole genome vs exome sequencing?
genome: do not know where in the genome the mutation is likely to be
exome: when it is known that the mutation likely lies in a gene - more defined (can use genome to get the same information, but its cheaper)
hypomorphic
leads to reduced gene product function
hypermorphic
leads to increased gene product function
when do synaptonemal complexes form?
at prophase I
what increases the risk of a nondisjunction event?
age of mother
decreased cohesion stability
note: increased homologous recombination would not increase the risk of a nondisjunction event
note: failure to depolymerize tubulin or loss of CDK1 activity would cause catastrophic meiosis and cell death
LOF mutation leads to
recessive phenotype
GOF mutation leads to
dominant phenotype
what is dad’s/mom’s age positively correlated with?
dad: de novo mutation rate
mom: non-disjunction events
if there is a mutation in the UTR, what is the expected outcome?
mutation in UTR => decreased stability of mRNA
can test to see if this protein is being expressed -> can indicate if this is a problem
haploinsufficiency
phenomenon where a diploid organism has only a single functional copy of a gene (with the other copy inactivated by mutation) and the single functional copy of the gene does not produce enough gene product (typically a protein) to bring about a wild-type condition, leading to an abnormal phenotype
