10
Genetic Variations in the Human Genome
Human genome rearrangements can occur by several mechanisms that include both
recombination and replication-based mechanisms. The latter can result in complex
genomic rearrangements. Genetic variations in the human genome are listed in Table 1.3.
Single Nucleotide Polymorphisms
Small stretches of DNA that differ in only one base are called single nucleotide poly-
morphisms (SNP) and serve to distinguish one individual’s genetic material from that
of another. SNPs comprise some 80 % of all known polymorphisms. Millions of
SNPs have been discovered in humans, and are available in public databases. Each
gene contains approximately fi ve coding SNPs, which likely effect the expression of
the currently estimated 20,000 genes. Identifi cation of SNPs is important as it helps in
understanding the genetic basis of common human diseases. In the absence of func-
tional information about which polymorphisms are biologically signifi cant, it is desir-
able to test the potential effect of all polymorphisms on drug response. Technologies
for SNP genotyping are described in Chap. 5. Potential uses of SNP markers are:
- Genome analysis for linkage studies
- Genome scan for association studies
- Candidate gene mapping
Table 1.3 Genetic variations in the human genomeVariation Features
Complex chromosomal
rearrangements (CCRs)
CCRs account for a large fraction of non-recurrent
rearrangements at a given locus
Copy number variation (CNV) DNA segments >1 kb in length, whose copy number varies
with respect to a reference genome. ~12 % of human
genes vary in DNA sequences they contain
Insertions and deletions in the
human genome (INDEL)
INDELS are an alternative form of natural genetic variation
that differs from SNPs
Interspersed repeated elements Long and short interspersed nuclear elements are a signifi cant
portion of human genome
Large scale variation in human
genome
Large portions of DNA can be repeated or missing for no
known reason in healthy persons
Segmental duplication Duplicons have >90 % sequence homology to another region
in the genome
Single nucleotide
polymorphisms (SNP)
SNPs are sequence variations at single base pair level with a
population frequency of >1 %
Structural variations (SVs) SVs involve kilobase- to megabase-sized deletions,
duplications, insertions, inversions, and complex
combinations of rearrangements
Tandem repeats Tandem sequences repetitions represent ~10 % of the genome
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1 Basic Aspects