Lecture 13 - Human genetics

Question 1

Describe genetic degeneracy

Answer 1

Occurrence of ‘silent’ variants

Question 2

What are alleles

Answer 2

Different forms of the same gene or genetic locus

Question 3

What is polymorphic loci

Answer 3

Several different alleles - no variation from person to person

Question 4

Describe a genetic marker

Answer 4

Variable providing information on specific DNA sequence at particular locus

Question 5

Describe disease susceptibility locus

Answer 5

Causal for particular disease

Question 6

How do genetic variants arise

Answer 6

DNA undergoes frequent chemical change - when replicated - most quickly repaired
Mutation is a failure of DNA repair

Question 7

Are mutations beneficial or harmful

Answer 7

No effect (neutral)
Beneficial
Harmful

Question 8

What is the difference between variants and mutations

Answer 8

Mutation - restrictive way - known genetic marker of disease or associated with susceptibility to disease
A new genetic variant created by mutation during replication or reproduction

Question 9

What are SNPs

Answer 9

Single Nucleotide Polymorphisms
-Base substitutions (NOT changes in # or arrangement)
Most common - unique genomic sequence arrangement for individuals
- No typically disease associated

Question 10

What is a DNA haplotype

Answer 10

Group of SNPs and genes inherited together from single parent
haplotype represents individuals combination of SNPs and gene - rarely separated by recombination (close proximity)

Question 11

What are the different types of point mutations

Answer 11

Silent - synonymous
Missense - (non-synonymous) - conservative (similar chemistry) - non-conservative
Nonsense - (premature stop)

Question 12

What is sickle cell disease

Answer 12

Non-conservative missense in beta-globin gene (HBB)

Question 13

What are the consequences of point mutations

Answer 13

Outside of gene have little to no effect on protein production or function
Non-coding - change amount of protein produced
coding region - change amino acid sequence

Question 14

Describe frameshift mutations

Answer 14

Insertion/deletion (InDel) - disrupt codon grouping -> completely different protein translation
- altered reading frames (stop codon -> loss of protein function)
- multiples of 3 BP causes no loss or gain of codons and corresponding acids

Question 15

What is an example of a frame shift mutation

Answer 15

Tay Sachs Disease
- inherited autosomal recessive
- progressively destroys nerve cells in brain and SC
- caused by frameshift mutations in HEXA gene

Question 16

What are copy number variations (VNTRs)

Answer 16

Variable number of tandem repeats or shot tandem repeats - minisatellites

Question 17

What is an examples of copy number variations

Answer 17

Huntington’s disease - excessive repetitions of cytosine-adenine-guanine nucleotide sequence

Question 18

Describe translocation

Answer 18

Movement on DNA stretch to new non-homologous chromosomal location (no molecular loss)
Genes at or near fusion boundaries become disrupted - result in formation of functionally fused abnormal gene products (‘chimeric proteins’)

Question 19

What is an example of translocation

Answer 19

Philadelphia chromosome
- Chronic Myeloid Leukaemia’s (CML)
- Produce BCR-ABL fusion protein
- Changes localisation of ABL kinase form nucleus to cytoplasm
activation of abnormal proliferation and survival pathways

Question 20

Describe nondisjunction

Answer 20

Failure of chromosomes to segregate correctly - too many or too few chromosomes