Lecture 30: Population Genetics 1

Question 1

What are microsatellites?

Answer 1

Microsatellites are a type of repetitive DNA.

• they occur due to slippage of DNA polymerase during replication
• they are distributed throughout the genome.
• many are located in non-coding parts of the human genome and are therefore biologically silent. This allows them to accumulate mutations unhindered over the generations and gives rise to variability which can be used for DNA fingerprinting and identification purposes.
• Other microsatellites are located in regulatory flanking or intronic regions of genes, or directly in codons of genes - microsatellite mutations in such cases can lead to phenotypic changes and diseases, notably in triplet expansion diseases such as fragile X syndrome and Huntington’s disease.

Question 2

What are other names for mini and micro-satellites?

Answer 2

• Minisatellites are also called VNTRs (Variable Number Tandem Repeats).
• Microsatellites are also called SSRs (Simple Sequence Repeats).

Question 3

What is the difference between minisatellites and microsatellites?

Answer 3

Minisatellites are bigger than microsatellites:

• minisatellites have repeats of 10-60bp
• microsatellites have repeats of 1-4bp

Minisatellites have more complex repeated sequences than microsatellites:

• minisatellites share a core motif GGGCAGGANG and telomeres consist of minisatellites (TTAGGG repeat)
• microsatellites most commonly have A or CA repeats

Question 4

How can mini and microsatellite alleles be detected?

Answer 4

After restriction enzyme digestion, gel electrophoresis, Southern blotting, and hybridization to the mini/microsatellite probe, researchers can obtain an autoradiograph.
With microsatellites, capillary electrophoresis is likely to be used.

Question 5

What is the most common type of DNA sequence variation?

Answer 5

SNPs, Single Nucleotide polymorphisms.

They occur about every 300-1000bp.

Question 6

How are SNPs genotyped now?

Answer 6

Identified from comparative DNA sequencing.

Huge numbers of SNPs can be genotyped with high throughput using microarrays.

Question 7

What is a haplotype?

Answer 7

Groups of loci that are close together are likely to share particular alleles because recombination will take a long time to “shuffle” the alleles.
We call groups of alleles found on an individual chromosome a haplotype.

Question 8

What is a haplotype network?

Answer 8

Haplotypes are joined in a haplotype network showing the relationships among the haplotypes. Each circle represents one of the haplotypes. The individual(s) carrying a specific haplotype are noted within each circle. Any two haplotypes differ at the loci noted on all of the branches connecting them.

e.g. the star-cluster haplotype is a haplotype much more common in the Y chromosome of Asian men than any other one haplotype. It is thought to be descended from Genghis Khan’s Y chromosome.

Question 9

What is the international HapMap project?

Answer 9

• Focussing on common SNPs (>1% of population show either allele)
• Tested 269 individuals from different populations
• Genotyped >106 SNPs (many more since Phase I)
• Defines a minimum number of SNPs to analyse for whole genome genotyping
• Allows for genome wide association studies