Genetics in Medicine 11-18

Question 1

What is meant by multifactorial inheritance?

Answer 1

Phenotype determined by action of many genes at different loci, have an additive effect. Usually environmental impact as well.

Question 2

Name some acquired diseases which show multi-factorial inheritance

Answer 2

Asthma, autism, cancer, diabetes, glaucoma, HTN, IBD, IHD, MS

Question 3

Why do pregnant women take folic acid supplements?

Answer 3

To reduce risk of neural tube defects

Question 4

What is a GWAS?

Answer 4

Genome wide association study. Examination of entire genome to assess gene variation between individuals.

Question 5

Give some examples of polygenic disease

Answer 5

Schizophrenia, type II diabetes, Alzheimer’s, age-related macular dystrophy

Question 6

Which hormone is related to fat cells?

Answer 6

Leptin

Question 7

What is a hydatiform mole?

Answer 7

Fertilisation with no oocyte, no embryo formation. Can develop into malignant trophoblastic tumour.

Question 8

What is parthenogenesis?

Answer 8

Benign ovarian teratomas derived from oocytes which have completed meiotic divisions.

Question 9

What is genomic imprinting?

Answer 9

Mechanism that ensures non-equivalence of maternal and paternal gene function. Epigenetic - not encoded in DNA sequence.

Question 10

Angelman and Prader-Willi syndrome both have a deletion of Chr 15 in the same region. Why do they have different phenotypes?

Answer 10

Depends on whether it is maternal or paternal chromosome that is disordered.
AS = maternal
PWS = paternal

Question 11

What is DNA methylation?

Answer 11

Post-synthetic DNA modification occurring at CG dinucleotides (CG islands). Carried out by DNA methyltransferases. Epigenetic - does not alter DNA sequence.

Question 12

What is monoallelic expression?

Answer 12

Epigenetic differences between maternal and paternal alleles. Only one allele is expressed.

Question 13

What is the foetal-maternal growth conflict and what affect does this have?

Answer 13

Mother needs to be able to deliver foetus so cannot be too big. Evolutionary advantage for father if foetus is larger. Maternal chromosome switches off genes promoting rapid growth, where as paternal chromosomes switch them on.

Question 14

What are the genetic differences between Beckwith-Wiedemann syndrome and Russel-Silver Syndrome?

Answer 14

Both same region of 11p15.5.
IGF-2 major foetal growth producer - only transcribed from paternal, chromosome. RSR: both copies unmethylated (inactivated). Growth retardation. BWS: foetal overgrowth.

Question 15

What is imprint switching?

Answer 15

Imprint must be remembered during somatic development but forgotten before gametogenesis so new parental imprint can be established.

Question 16

Briefly explain X inactivation.

Answer 16

Females have 2 copies of X chromosome - dose overload. Epigenetic silencing of one X chromosome allows mono allelic expression. Random choice of chromosome, different in different cells.

Question 17

Name a CF drug that works for some genotypes but not others?

Answer 17

Ivacaftor. Significant improvement in patients with G551D, but no improvement in homozygous DF508del.

Question 18

Which genes may influence warfarin activity?

Answer 18

CYP2C( (cytochrome P450) and vit K oxidreductase complex-1 (VKORC1)

Question 19

Name a drug used to target breast cancers with HER2 over-expression

Answer 19

Trastuzumab

Question 20

What type of inheritance does Huntington’s Disease show, and what is the genetic abnormality?

Answer 20

AD inheritance.

Expansion of CAG repeats, >40, in HTT gene.

Question 21

What is anticipation?

Answer 21

Onset of disorder occurs at earlier age as it is passed from one generation to next. Associated with triplet repeat disorders.