Human genetic variations include single nucleotide substitutions, tandem repeats, insertions and deletions, copy number variations, inversions, and translocations. These variations differ in DNA sequence and range in size from single nucleotides to megabases. The most common type is single nucleotide polymorphisms (SNPs), which represent differences in single nucleotides occurring about once every 1,000 nucleotides. SNPs can cause diseases like sickle cell anemia. Tandem repeats and copy number variations can also lead to diseases if DNA is misaligned during replication. Inversions and translocations occur when chromosomes break and rearrange, which can cause cancers, infertility, or Down syndrome. Variants in coding regions can be silent, nonsense, or missense mutations affecting protein function

1. HUMAN GENOME VARIATION
By
SYEDA SADAF WAJAHAT

2. HUMAN GENOME VARIATION
■ Human genetic variations are the differences in DNA sequence within the
genome of individuals in populations.
■ Genetic variations in the human genome are of many types, including
single nucleotide substitutions; tandem repeats; insertions and deletions
(indels); copy number variations (CNVs); inversions and translocations.
■ These genetic variations span a spectrum of sizes from single nucleotides
to mega bases.

3. SINGLE NUCLEOTIDE POLYMORPHISM (SNP)
■ Single nucleotide polymorphisms (SNPs), are the most common type of
genetic variation among people.
■ Each SNPs represents a difference in a single
nucleotide.
■ SNPs occur almost once in every 1,000 nucleotides
on average.
■ SNPs causes a wide range of diseases like Sickle cell anemia, B-thalassemia
and Cystic fibrosis.

4. TANDEM REPEATS
■ Tandem repeats contain many copies of the same short sequence over
and over, so it is easy for the two strands of DNA to get misaligned in this
local region.
■ If the strands are mis paired, then DNA replicating enzymes can either
clip off some of the repeats or add extra repeats.
■ Examples: Huntington’s disease, Kennedy’s disease, Myotonic dystrophy.

5. INSERTIONS AND DELETIONS
■ An insertion changes the number of DNA bases in a gene by adding a
piece of DNA. As a result, the protein made by the gene may not function
properly.
■ A deletion changes the number of DNA bases by removing a piece of DNA.
The deleted DNA may alter the function of the resulting protein(s).

6. COPY NUMBER VARIATIONS (CNVs)
■ Copy number variation is a type of structural variation where a stretch of
DNA is duplicated and sometimes even triplicated or quadruplicated at
the chromosomal region in some people,
■ Examples: Alzheimer’s and Schizophrenia diseases.

7. INVERSION
■ An inversion involves the breakage of a chromosome in two places; the
resulting piece of DNA is reversed and re-inserted into the chromosome.
■ It has been associated with congenital anomalies, growth retardation,
infertility, recurrent pregnancy loss, and cancer.

8. TRANSLOCATION
■ A translocation occurs when a piece of one chromosome breaks off and
attaches to another chromosome.
■ It is of two types balanced translocation (no genetic
material is gain or loss) and unbalanced translocation
(there is a gain or loss of genetic material).
■ Examples: Cancers, Infertility, Down syndrome.

9. EFFECTS OF VARIANTS IN CODING REGIONS
■ If a variant falls within a coding region, it can be categorized as:
1. Synonymous/Silent mutation: Due to redundancies in the genetic code,
many nucleotide changes will not change the amino acid sequence, for
example a GCT to GCC change would still encode an alanine.
2. Nonsense mutation: These turn a coding codon, such as GGA glycine, to a
stop codon, e.g. TGA. This will result in a truncated protein.
3. Missense/Nonsynonymous mutation: This change results in a change in
amino acid, for example ACC threonine to AAC asparagine.