Definitions

Question 1

Anticipation

Answer 1

Where the signs and symptoms of a genetic condition become more severe and appear at an earlier stage as the disorder is passed from one generation to the next e.g. a trinucleotide repeat syndrome such as FRAX or myotonic dystrophy

Question 2

Age related mosacisim

Answer 2

The accumulation of somatic or germline mutations over the course of a person’s life resulting in mosaicism. e.g. loss of X in older women.

Question 3

Variable expressivity

Answer 3

When a phenotype is expressed differently in individuals with the same genotype. DIFFERENT TO PENETRANCE. e.g. Marfans or Waardenburg syndrome.

Question 4

Penetrance

Answer 4

The proportion of individuals carrying a particular variant of a gene who also express that associated trait/phenotype e.g 95% penetrance = 95% of those with the mutated gene will show the clinical features and 5% will not.
100% - termed complete penetrance.
Incomplete or reduced penetrance e.g. BRCA1 mutation (80% penetrance)

Question 5

Attributable risk

Answer 5

Proportion of total risk that can be attributed to the presence of the allele. Many alleles have been shown to be associated with some forms of cancer, but there are cases where the cancer has arisen without an individual having that allele.

Question 6

Sex-limiting genes

Answer 6

Genes which are present in both sexes, but are expressed only in one sex and cause different traits or phenotypes e.g. lactation in women. Sex limiting gene diseases are autosomal diseases (different to sex linked diseases which affect genes of the X and Y chromosomes).

Question 7

Epistasis

Answer 7

Interaction of non-allelic genes, where one masks the effective of another. e.g the gene for albinism will mask the gene for coding for hair colour.
Also if a gene upstream of another gene. If gene A is upstream of gene B in a pathway and isn’t functioning, gene B will lose all its function too. Gene B is hypostatic and gene A is epistatic.

Question 8

Pleiotrophy

Answer 8

One gene affects two or more unrelated phenotypes e.g. phenylketonuria (PKU) - phenylalanine hydroxylase enzyme gene which converts phenyalanine to tyrosine. High levels of phenylalanine are toxic to a newborn or infant and can cause MR and abnormal gait and posture. Failure to convert phenylalanine to tyrosine can result in less pigmentation produced causing fair hair and skin.

Question 9

Antagonist pleiotrophy

Answer 9

A gene having seemly competing effects e.g. p53 which suppresses cancer, but also suppresses stem cells which replenishes worn out tissue.

Question 10

Amorphic mutation

Answer 10

mutation that results in complete loss of function

Question 11

Hypomorphic mutation

Answer 11

mutation that causes partial loss of gene function

Question 12

Hypermorphic mutation

Answer 12

mutation that causes an increased level of gene function

Question 13

Antimorphic mutation

Answer 13

aka dominant negative mutation. Have the opposite effect on the gene function

Question 14

Neomorphic mutation

Answer 14

Mutation that causes a gain of a new function from normal activity

Question 15

Hemizygous

Answer 15

A gene with no counterpart allele e.g. men for genes on the X chromosome

Question 16

Compound heterozygous

Answer 16

the presence of two different alleles at a particular gene locus on a chromosome pair that have different mutations.

Question 17

Haploinsufficieny

Answer 17

Where half the amount of gene product is not enough to maintain normal function.