Genetic Variation and Population Genetics

DNA Sequence Variations and Tandem Repeats

Frameshift mutations involve a nonmultiple of $3$ base pairs and can alter exon or RNA gene function, though most mutations reside within the non-coding $98.5\text{\%}$ of the genome. Variable numbers of tandem repeats (VNTRs) consist of head-to-tail repetitive DNA sequences. Microsatellites consist of repeats of $1$ to $9\text{ base pairs}$, mutate very slowly, and remain stable across $10$ to $20\text{ generations}$, serving as reliable individual markers for forensic DNA. Mini satellites contain larger repeats ranging from $10\text{ base pairs}$ up to about $100\text{ base pairs}$.

Copy Number Variants

Copy number variants (CNVs) are genomic segments spanning from $500\text{ base pairs}$ up to $1 C00 C00\text{ base pairs}$ that are duplicated or deleted head-to-tail. A deletion removing a large region can eliminate $10$ to $20\text{ genes}$, causing recessive lethality or leaving a person with a single remaining allele. If this region contains a tumor suppressor gene, losing one allele significantly elevates cancer susceptibility. Conversely, a duplication creates $3\text{ copies}$ of every gene in that region; if it contains a proto-oncogene, overproduction of the gene product can drive dominant phenotypic effects toward cancer.

Classification of Point Mutations and SNPs

Point mutations generated in maternal or paternal germlines result in roughly $200\text{ private mutations}$ unique to an individual at very low allele frequencies. Changes present at frequencies up to $1\text{\%}$ are termed variants, whereas common allele frequencies exceeding $1\text{\%}$ are classified as polymorphisms. Single nucleotide polymorphisms (SNPs) occur approximately once every $1000\text{ base pairs}$, resulting in $3 C00 C00\text{ SNP sites}$ scattered across a $3 C00 C00 C00\text{ base pair}$ haploid genome. Rare SNPs have allele frequencies of $1\text{\%}$ to $5\text{\%}$, while common SNPs have frequencies of $5\text{\%}$ or higher.

Allele Frequency Calculations

Allele frequency represents the proportion of a specific allele relative to the total number of alleles in a gene pool. In a sample population of $16\text{ frogs}$ containing $5$ homozygous big A ($AA$), $3$ homozygous small a ($aa$), and $8$ heterozygous ($Aa$) individuals, the total allele count is $32\text{ alleles}$. The allele frequency of allele big A ($p$) is calculated as $p = \frac{18}{32} = 0.56$, and the frequency of allele small a ($q$) is $q = \frac{14}{32} = 0.44$. For biallelic markers, calculations must always be performed in decimals and satisfy the relationship $p + q = 1$.

Evolution and Hardy-Weinberg Equilibrium

Evolution is defined mathematically as a change in allele frequency within a gene pool over time (Dobzanski, $1975$). Hardy-Weinberg equilibrium establishes the predicted genotype frequencies at which allele frequencies $p$ and $q$ remain stable in a non-evolving population. The equilibrium was formulated independently by Hardy at Cambridge and Oxford—who spent approximately $20\text{ minutes}$ resolving a query from Rachel Punnett regarding a postulate by a statistician from Haddington, East Of Edinburgh—and Weinberg, an obstetrician and gynecologist.

Questions & Discussion

During discussion, human traits and clinical conditions associated with microsatellites were addressed. Huntington's disease is an example of a human condition caused by instability in a $3\text{ base pair}$ microsatellite repeat consisting of CAG. Additionally, the fundamental reason why single nucleotide polymorphisms in populations are predominantly biallelic remains an unresolved question under consideration.