Lecture 14 - Medical Genetics: Consequences of Genomic Alteration

Question 1

Beta-Thalassemia?

Answer 1

inherited blood disorders caused by reduced synthesis of beta haemaglobin chains - autosomal recessive mutation in HBB gene on chromosome 11

Question 2

Down Syndrome causes?

Answer 2

chromosomal disorder: non-disjunction metaphase I, translocations (rare)

Question 3

Multifactoral genetic disorders?

Answer 3

interaction of multiple genes causing single phenotype, most common and least understood e.g. diabetes

Question 4

Somatic Cell Genetic Disorders?

Answer 4

arise in specific somatic cells, as opposed to germ cells, not inherited, e.g. cancer

Question 5

Mutation definition?

Answer 5

Any alteration in DNA from its natural state; may be disease-causing or a benign normal variant

Question 6

Polymorphism definition?

Answer 6

Natural variations in genomic DNA sequencing that usualy have no obvious adverse effects on the individual and occur with relatively high frequency at a population level

Question 7

Types of mutation?

Answer 7

silent, missense, nonsense, frameshift, splice donor/acceptor

Question 8

Determining if a CNA change is pathogenic?

Answer 8

functionally important site of missense, RNA splicing affected, predicted protein truncated, does the change segregate disease in the family

Question 9

Loss-of-function Mutations?

Answer 9

reduced activity, null allele, haploinsufficiency, dominant negative

Question 10

Variable Penetrance?

Answer 10

failure of dominant condition to manifest in all mutations

Question 11

Variable expression?

Answer 11

signs and symptoms differ among individuals

Question 12

Allelic heterogeneity?

Answer 12

different mutations at same locus e.g. cycstic fibrosis has >1000 mutations in CFTR gene

Question 13

Locus heterogeneity?

Answer 13

mutations at different loci e.g. retinitis pigmentosa