Human Variability & Evolution

Question 1

Relationship between reproduction and population diversity

Answer 1

Reproduction (particularly recombination) introduces genetic differences. Allowing for evolution of new traits. Better adapted to enviornmental conditions (eg disease prevention) survive to reproduce, pushing survival traits to rest of population

Question 2

Aneuploidy Def

Answer 2

Large scale germline genetic variation. 1(+) individual chromosomes either (a) have an extra copy or (b) are missing (ie In diploids there’s either (a) 3 chromosomal copies or (b) 1).

Question 3

Down Syndrome Outline

Answer 3

aka trisomy 21. Example of Aneuploidy. 3 copies of chromosome 21 result in greater expression of it’s genes; lower cancer (solid tumour) risk but higher Alzheimer’s

Question 4

Turner’s Syndrome Outline

Answer 4

Deletion of part of/full X chromosome in females. Aneuploidy. X genes are less expressed; infertility, short stature, deformities of heart

Question 5

Translocation Def

Answer 5

Large scale germline genetic variation. Exchange of DNA in meiosis between 2 different chromosomes. Consequence severity depends on event (if in non-coding region no effect, if cut in coding region reduced gene expression)

Question 6

Philadelphia Chromosome Outline

Answer 6

Translocation Example. When chromosome is cut off at band 9 gene expression of ALB1 (cell division repressor) is cut and combined with BCR1 (cell signaller, chromosome 22). Results in formation of constitutive oncogene causing chronic myeloid leukemia

Question 7

Copy Number Variants Def

Answer 7

Large scale germline genetic variation. Deletions/duplications >1,000 base pairs on DNA (up to several million). Typically benign (and common) but if exceeding 1 million bps tend to be pathogenic

Question 8

Huntington’s Disease Outline

Answer 8

Autosomal dominant CNV. Expanded CAG sequence in HTT gene results in toxic protein expansion. Leads to neuronal dysfunction affecting cognitive processing and movement. Earlier onset in later generation (CAG region keeps getting bigger)

Question 9

What is the cause of CNVs

Answer 9

DNA polymerase slippage causing misalignment of DNA strand pairs. Resulting in; (a) misreading of a repeated sequence, where only 1 complementary sequence is produced where there should have been multiple (=shorter chain) or (b) production of extra sequence is produced as polymerase rereads a section (=longer chain, rarer event)

Question 10

Microsatellite Def

Answer 10

Small germline genetic variation. 2-5bp repeats in DNA sequence (mainly non-coding). Quite common and most are benign

Question 11

Single Nucleotide Polymorphism (SNP) Def

Answer 11

Small germline variation. Change of a single base pair (as compared to reference sequence). All individuals contain millions. Mainly benign but some have severe consequences

Question 12

Sickle Cell Anemia Outline

Answer 12

Caused by a recessively inherited SNP in HBB gene resulting in a VAL aa replacing GLU in beta-globin subunit. Causes deformed cells resulting in severe pain and bloackage. Has heterozygote advantage in regions with high malaria risk (as mutation has higher malarial survival rates)

Question 13

Insertions and Deletions (InDels Outline)

Answer 13

Small DNA sections (1-3 bps) that are deleted/duplicated. Everyone carries multiple in their genome. Vast majority are benign, risk of frameshift

Question 14

Cystic Fibrosis Outline

Answer 14

Recessively inherited (heterogenous) CFTR protein mutations. Insertion of T and position 3905 causes frameshift resulting in damaged protein (Cl ion channel)

Question 15

Pathogenic Mutations Outline

Answer 15

Changes in gene function that result in disease. Altered levels/timings of expression, alter splicing, different amino acid sequence and difefrent length of protein chain (non-sense mutation)

Question 16

Features of large scale pathogenic variation

Answer 16

Largely different levels of gene expression. Gene protein levels are altered

Question 17

Features of small scale pathogenic variation

Answer 17

Changes in amino acid sequence. Skipping/intro of exons, premature translation stops

Question 18

Frameshift Outline

Answer 18

DNA polymerase in 1 bp off reading sequence correctly, wrong amino acid produced (different structure, chemical properties and overall function)

Question 19

Genetic Variation in Malignant Cells Outline

Answer 19

Genomically unstable, allowing greater cancer evolution (survival advantage). Genetic mutations induce cancer and cancer cells create further mutations.

Question 20

Function of cancer ‘driver’ mutations

Answer 20

continue genomic instability, bypassing of safety mechanisms (inhibition signals), rapid growth/division and metastasis

Question 21

Passive Mutations Outline

Answer 21

Mutation in cells that don’t aid cancer growth

Question 22

When can intrinsic mutation processes effect cancer risk

Answer 22

Gestation (division after fertilisation) to chemotherapy resistant reoccurrence

Question 23

When can enviornmental exposures effect cancer risk

Answer 23

Childhood to chemotherapy ressistant reoccurance

Question 24

When can mutator phenotype effect cancer risk

Answer 24

Benign tumour stages to chemotherpy ressistant reoccurance

Question 25

Cancer Cell Clones

Answer 25

Different cancers in different tissues. 1 clone may be seneitive to 1 pharamcological agent and not another. requires profileof genetic characterisation