Personalized Genomics and the Human Genome

Vocabulary practice flashcards covering personalized genomics, comparative hominid cytogenetics, sequence divergence rates, indels, copy number variations (CNVs), and global population genetic variation.

Whole Genome Sequencing (WGS)

A genetic testing approach that analyzes the entire DNA sequence of a tumor to detect every cancer-causing mutation, enabling clinicians to identify the most effective targeted therapies.

Human Chromosome 2 Fusion

A unique chromosomal fusion event in the human lineage where two ancestral ape chromosomes (designated $2\text{A}$ and $2\text{B}$ in chimpanzees, gorillas, and orangutans) fused end-to-end to form human chromosome $2$.

Human-Chimpanzee Divergence Time

The evolutionary split between humans ($\text{Homo sapiens}$) and chimpanzees ($\text{Pan troglodytes}$) that occurred approximately $6\text{ million years ago}$ ($6\text{ mya}$), representing an effective accumulation of differences across $12\text{ million years}$.

Pseudogene Divergence Rate (Human/Chimpanzee)

The genomic region with the highest observed rate of nucleotide substitutions between humans and chimpanzees ($\bar{K} = 0.020$ across $752.4\,\text{Kb}$), reflecting neutral evolution in non-functional DNA.

$5'$ Untranslated Region Divergence Rate (Human/Chimpanzee)

The genomic region exhibiting the lowest substitution rate between humans and chimpanzees ($\bar{K} = 0.001$ across $68.7\,\text{Kb}$) due to selective constraints.

Indel Bias in Human Pseudogenes

The pattern identified by Zhang & Gerstein (2003) showing that deletions ($3,740$) significantly outnumber insertions ($1,291$) among events less than $60\,\text{bp}$ across $700,000\,\text{bp}$ of human pseudogenes.

Copy Number Variations (CNVs)

Large-scale structural deletions and insertions spanning thousands to millions of base pairs (or criteria of $>50\,\text{bp}$ to $>500\,\text{bp}$) that, despite their size, predominantly represent benign variation rather than disease states.

Average Human Inter-Individual CNV Difference

The finding (Sebat et al., 2004) that any two unrelated individuals differ on average by $11\text{ CNVs}$ with a mean length of $465\,\text{kb}$, creating a net difference of approximately $5,115,000\,\text{bp}$.

Escherichia coli Genome Equivalence in CNVs

A comparative benchmark ($\approx 4,686,000\,\text{bp}$) demonstrating that the average CNV sequence difference between two humans ($5,115,000\,\text{bp}$) exceeds the entire genome size of an organism like E. coli.

Asymmetry of CNV Gains vs. Losses

The genomic distribution reported by Zarrei et al. (2015) in which deletions outnumber duplications ($12,000\text{--}23,000$ losses vs. $1,000\text{--}3,000$ gains), but gains are significantly larger in average length ($36\text{--}55\,\text{Kb}$ vs. $8\text{--}9\,\text{Kb}$).

Average Human-to-Human SNP Divergence

The baseline rate of single nucleotide differences between two unrelated humans, occurring at approximately $1\text{ in }1000\,\text{bp}$, yielding about $(1/1000) \times (6 \times 10^9) = 6 \times 10^6$ differences across a diploid genome.

dbSNP

An NCBI database cataloging human single nucleotide variations (SNVs), microsatellites, and small-scale indels alongside population frequencies, molecular consequences, and RefSeq mapping data.

The 1000 Genomes Project

A landmark global study that sequenced $2,504\text{ individuals}$ across $26\text{ populations}$, characterizing over $88\text{ million variants}$ ($84.7\text{ million SNPs}$, $3.6\text{ million short indels}$, and $60,000\text{ structural variants}$).

Reference Genome Divergence per Individual

The standard divergence metric showing that a typical individual human genome differs from the human reference genome at $4\text{ to }5\text{ million sites}$, of which more than $99.9\%$ are SNPs and short indels.

Population Genomics - there is no “The human genome”

The field of study examining the collective genetic diversity of entire populations, grounded in the reality that high inter-individual variation precludes the existence of a single static 'human genome.'