CBCL I

Question 1

Discriminate between a gain of function mutation and a loss of function mutation

Answer 1

Gain of Function: Produce increased amount or increased activity of the product. Ex: Myotonic dystrophy

Loss of Function: Produce either reduced amount or reduced activity of the product. No production= null allele.

Usually, one good allele will be sufficient and phenotype will not be altered. Recessive loss of function.

Haploinsufficiency: a 50% product level results in altered phenotype. Dominant loss of function

Question 2

Haploinsufficiency

Answer 2

A 50% product level results in altered phenotype. Dominant loss of function

Question 3

Describe X-linked Inheritance

Answer 3

Genes on the x chromosome. Females receive one from mom and one from dad. Males only receive X chromosomes from mom.

X-Linked Recessive: Mostly affects males, all daughters of affected males are carriers, females only affected if they have structural cytogenic X abnormality, are 45X, or have both carrier mother and carrier father. No male-male transmission. Carrier females have 50% risk of passing it on to child.

X-Linked Dominant: Both males and females affected, more females evident. Females usually less severely affected due to random X inactivation and mosaicism, no male-male transmission.

Question 4

Contrast autosomal dominant and autosomal recessive mutations

Answer 4

Autosomal Dominant: males and females equally affected, equally capable of transmitting trait, affected person usually has at least one affected parent, 50% probability of transmitting trait to offspring, gene product is commonly a non-enzymatic protein

Autosomal Recessive: both parents of child are usually asymptomatic carriers, cansanguineous partners increase risk of affected children, one affected child means 25% chance of future affected children, if unaffected- 2/3 risk of being a carrier. Gene product is commonly an enzyme.

Question 5

Homozygote

Answer 5

Individual has two identical alleles for a gene

Question 6

Heterozygote

Answer 6

Individual has two different alleles for a gene

Question 7

Compound heterozygote

Answer 7

Individual has two different mutant alleles for a gene

Question 8

Haplotype

Answer 8

Group of genes that were inherited from a single parent.

Question 9

Evaluate the difference between whole-genome and whole-exome sequencing

Answer 9

Whole-genome is more expensive and provides much more information on indiviual. Whole-exome is cheaper, but exons are only 2% of entire genome.

Question 10

Anticipation

Answer 10

Phenotype or prognosis worsens as the family lineage continues.

Question 11

Define & distinguish germline and somatic mosaicism

Answer 11

Germline mosaicism: mutation involves germline cells and can be passed to offspring.

Somatic mosaicism: mutation only involves somatic cells and cannot be passed on.

If the mutation arose in a somatic cell during development, the population of cells with this mutation might be too small to cause an observable phenotype.

Question 12

Penetrance

Answer 12

Likelihood that a characteristic manifests itself

Question 13

Variable Expressivity

Answer 13

Different features of a disorder manifesting in different affected individuals

Question 14

Hardy-Weinberg Equilibrium

Answer 14

Equations:

p = AA + ½Aa

q = aa + ½Aa

p + q = 1

(p + q)² = 1

p² + 2pq + q² = 1

Question 15

Phenocopy

Answer 15

Phenocopy: a family of a phenotype that is similar to a particular disorder, but developed in absence of an inherited genotype

Question 16

Heteroplasmy

Answer 16

Heteroplasmy: mixed population of normal and abnormal mitochondrial genomes within each cell.