Question

1. Genetic variation is the difference in DNA sequences between individuals within a population. The human genome has about 3 × 10⁹ base pairs of DNA, and between any two humans, the amount of genetic variation is about 0.1%. In other words, about 1 bp in every 1,000 bp of DNA will be different between two random individuals. Any two individuals have about 6 × 10⁶ base pairs that are different. Therefore, we can say that there is considerable genetic variation in humans and it is important to understand every kind of genetic variation and to develop specialized techniques to analyze these variations. Only then, we can identify and relate these variations with human health and disease.

1. Please consider our whole genome and write and briefly explain every possible type of human genetic variation that you can think of.
2. Choose two variations from part (i) and state two different techniques to identify these two variations. Please explain briefly how these techniques can detect these variations.
3. What may be the effect of genetic variations, if they are found in protein coding regions of genes?

Answer 1

1) As mentioned above human genetic variation, is the measure of an individual's differences in DNA against the population. Listed below are a list of genetic variations that occur in the human genome and a short definition of their aspects

1. The most common, single nucleotide polymorphisms (SNPs) are a change in a single nucleotide position compared to the rest of the population.
2. There are also structural variations to entire chromosomes.
3. Deletions - deletion of a part of a chromosome during replication
4. Inversions-Inverting the segment polarity in chromosomes, a single chromosome breaks and rearranges within itself
5. Duplications- repetitions of part of the genome during errors in DNA division
6. These changes occur mainly due to errors in homologous recombination and DNA replication
7. Copy number variations- repeated structures in genomes
8. Variable tandem repeats - short repeated nucleotides like AT repeats occupy a large part of the genome.

2) The two variations that could be chosen are

Duplications - duplications can be of genes, entire chromosomes or even genomes

If it is a genome duplication, using a DNA staining dye and visualizing karyotype under a microscope is a valid identification

If it is a gene duplication event, then the number of transcripts it has will be changed. Then whole-genome sequencing is a valid option to find out all of the duplication events. Sequencing is a process that determines the A, T, C, G sequence of the genome.

Single nucleotide polymorphisms are found out by DNA footprinting

One example is PCR (polymerase chain reaction), where we design primers for a particular SNP and we amplify the sequence, which will confirm its presence.

3) If there is a deletion within an exon it might affect the folding of the protein making it a loss of function mutation. Or it might impart a new trait which would be a gain of function mutation. Coding region mutations, especially more than a single nucleotide have one of the above effects.