CBCL1: Mendelian Inheritance and Chromosomal Disorders

Question 1

incomplete penetrance

Answer 1

patient has the mutation but no disease

Question 2

non-penetrance

Answer 2

no phenotype because of modifying factors/non-genetic mechanisms, but the genetic mutation is present

Question 3

GOF

Answer 3

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

Question 4

LOF

Answer 4

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

Question 5

dominant negative

Answer 5

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

Question 6

recessive negative

Answer 6

abnormal protein that is inherited in a negative fashion (most mutant alleles)

Question 7

what causes somatic mosaicism?

Answer 7

two different tissues having different karyotypes -> suggests an error during mitosis in the early embryo

Question 8

obligate carrier

Answer 8

an individual who is a carrier of a mutation but does not have the phenotype

characteristic of non-penetrant disorders

Question 9

variable expressivity

Answer 9

range of signs and symptoms occurring in different people with the same genetic condition

“difference in symptoms”

characteristic of non-penetrant disorders

Question 10

locus heterogeneity

Answer 10

mutation in different genes may explain one variant phenotype

Question 11

allelic heterogeneity

Answer 11

different alleles in the same gene can cause a similar variant phenotype

Question 12

anticipation

Answer 12

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

Question 13

haplotype

Answer 13

a set of polymorphisms in different genes that reside closely on a given chromosome and are often inherited together

can correlate with disease severity

Question 14

null allele

Answer 14

no product or function results from the allele

Question 15

when to use whole genome vs exome sequencing?

Answer 15

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)

Question 16

hypomorphic

Answer 16

leads to reduced gene product function

Question 17

hypermorphic

Answer 17

leads to increased gene product function

Question 18

when do synaptonemal complexes form?

Answer 18

at prophase I

Question 19

what increases the risk of a nondisjunction event?

Answer 19

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

Question 20

LOF mutation leads to

Answer 20

recessive phenotype

Question 21

GOF mutation leads to

Answer 21

dominant phenotype

Question 22

what is dad’s/mom’s age positively correlated with?

Answer 22

dad: de novo mutation rate
mom: non-disjunction events

Question 23

if there is a mutation in the UTR, what is the expected outcome?

Answer 23

mutation in UTR => decreased stability of mRNA

can test to see if this protein is being expressed -> can indicate if this is a problem

Question 24

haploinsufficiency

Answer 24

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