‫‪Lecture‬‬

‫‪3rd Stage‬‬ ‫الجامعـــة التقنيـــة الجنوبيــــة‬

‫‪05‬‬
‫‪Medical Genetics‬‬ ‫كلية التقنيات الصحية والطبيـة‬
‫‪2021-2022‬‬ ‫قســـم التحليـــالت المرضيــــة‬

‫‪Genetic Variation‬‬

‫‪Dr. Hussam S. Aziz‬‬

‫‪MSc. Medical Genetics‬‬
Introduction
▪ Genetic variation is a term used to describe the variation in
the DNA sequence in each of our genomes

▪ Genetic variation is what makes us all unique, whether in

terms of hair color, skin color or even the shape of our faces

▪ Individuals of a species have similar characteristics but they

are rarely identical, the difference between them is called
variation

▪ Genetic variation is a result of subtle differences in our DNA 2

Some Facts
▪ Normal human somatic cell contains 46 chromosome

▪ Each chromosome is composed of a continuous, double

stranded DNA molecule

▪ DNA molecule is made up of nucleotides and is measured by

base pair (bp)

▪ Human nuclear genome contains approximately 3280 million

base pairs (3x10^9 bp) 3
Glossary
▪ Genome the entire set of genetic instructions found in a cell. In
humans, the genome consists of 23 pairs of chromosomes,
found in the nucleus, as well as a small chromosome found in
the mitochondria. Each set of 23 chromosomes contains
approximately 3.2 billion bases of DNA sequence

▪ Gene is the basic physical and functional unit of heredity.

Genes are made up of DNA with a specific sequence to encode
a certain protein or RNA. Every gene is responsible for a
certain character. Every person has 2 copies from every gene,
one copy from the mother and one copy from the father
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Glossary (cont.)
▪ Allele is one of two or more forms of a given gene variant,
e.g. alleles for skin colors, eye colors, etc. An individual
inherits two alleles for each gene, one from each parent
▪ If the two alleles are the same, the individual is said to be
homozygous for that gene
▪ If the two alleles are different, the individual is said to be
heterozygous for that gene
▪ Trait is a characteristic that makes one person different
from another. Each trait results from the interaction
between the two alleles
▪ Phenotype is the sum of individual's observable traits, such
as height, eye color, blood type, etc.
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▪ Genotype is the genetic contribution to the phenotype
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Human Genome
▪ Human genome consists of about 3.2 billion bases
▪ There are currently 30,073 identified genes in the human
genome:
▪ 21,598 protein encoding genes

▪ 8,475 RNA genes (regulatory RNA)

▪ In fact, only 1.1% of the human genome is actually protein
coding DNA
▪ Another 4% are also important, consisting of gene-regulatory
sequences and RNA genes
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Human Genome (cont.)
▪ A large proportion of the non-coding DNA (around 20% of
the genome) consists of introns and untranslated regions
(UTR) of genes, in addition to other non-coding gene–related
sequences such as pseudogenes

▪ The majority of the non-coding DNA (around 75% of the

genome) is extra-genic, and much of this DNA (55% of the
genome) consists of repeated sequences

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Genetic Variation
▪ No two people are genetically identical (EXCEPT for identical
twins)

▪ Any two people have about 6X10^6 base pairs which are
different; this may seem like a lot, but in fact is only 0.1% of
the entire human genome

▪ Any two individuals are 99.9% identical in their DNA

▪ That 0.1% is very important in defining our differences 11

Identical twins develop from the same fertilized ovum,
so the DNA in their cell is the same

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Genetic Variation (cont.)
▪ The 0.1% of unique DNA, plus the interaction of genetic and
environmental factors, is what leads to our different
phenotypic features

▪ Human genetics is the scientific study of inherited human

variation

▪ We study this variation in order to better understand

ourselves as a species and use this knowledge to improve
our health and well-being
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 “We all are very similar…

but we all are very different…”

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Sources of Genetic Variation
1. Polymorphisims: Differences in individual DNA which are not
mutations (not pathogenic); polymorphisms include:
▪ Single nucleotide polymorphisms (SNP)
▪ Copy number variations

2. Mutations: Differences in DNA sequences that are pathogenic

(produce genetic diseases). There are many types of
mutations:
▪ Chromosomal disorders
▪ Large mutations
▪ Point mutations 15
Single Nucleotide Polymorphism (SNP)
▪ SNP is a variation at a single position in a DNA sequence
among individuals
▪ For example, two sequenced DNA fragments from two
different individuals:
▪ ….AAGCCTA….
▪ ….AAGCATA…..
contain a difference in a single nucleotide
▪ Are the most common source of variation, occurring about
once every 1,000 bases or so
▪ SNPs are not pathogenic → do not lead to genetic diseases
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Single Nucleotide Polymorphism (SNP) (cont.)
▪ Single nucleotide polymorphisms may fall within coding
sequences of genes (exons), non-coding regions of genes
(introns), or in the intergenic regions between genes
▪ SNPs within a coding sequence will not necessarily change the
amino acid sequence of the protein that is produced, due to
degeneracy of the genetic code, e.g. both CCA and CCG encode
for proline
▪ SNPs might also lead to non-pathological variations in
phenotypic features between individuals, such as the color of
skin, eyes, hair, height, etc.
▪ Researches showed that SNPs have fixed locations in the
genome, every SNP is given a specific number, and today there
are special databases (websites) for researchers to get
information about different SNPs 18
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 Copy Number Variation (CNV)
▪ Certain regions in the genome (55% of the genome) have
repeated sequences
▪ Divided into two types:
▪ Short tandem repeats (STR): adjacent short sequences (1, 2,
3, 4, or 5 nucleotides) repeated for a certain (n) number of
times, e.g. AAAAAA…., AC AC AC AC…., CTG CTG CTG CTG…
▪ Interspersed (single) repeats: longer sequences repeated for
one time. Can be subdivided according to the length into:
▪ Short interspersed nuclear elements (SINES) are below 500
bp
▪ Long interspersed nuclear elements (LINES) from 500 bp to
10 kb 29
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Short Tandem Repeats (STR)
▪ There can be variation (polymorphism) in the number of repeats
at a certain positions (locus) of the genome between different
individuals, e.g. at a certain locus, person A has 6 repeats, and
person B has 10 repeats
▪ The variation in copy number leads to different alleles
(alternative copies) of that sequence
▪ Every individual has 2 copies (alleles) of the STR, a copy from
each parent
▪ Homozygous: both alleles in the individual have the same
length
▪ Heterozygous: alleles in the individual have different lengths
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Short Tandem Repeats (STR) (cont.)
▪ STRs can be divided into 3 types according to the number of
repeats: Microsatellites, Minisatellites, and Macrosatellites
▪ Microsatellites: are short sequences repeated for less than 1
kb (1000 bp). They are found in certain loci in the genome
and the variation in copy number can be used for DNA
profiling in:
▪ Forensics: to identify individuals identities from body
tissues (hair, semen, etc.) left at crime scenes
▪ Paternity identification
▪ Linkage analysis: to track the parental source of a certain
(diseased) gene
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Short Tandem Repeats (cont.)
▪ Minisatellite: repeat arrays are usually 1–30 kb in length and
have longer repeat motifs than the microsatellite repeats. They
again show marked variation in repeat number. As minisatellites
are generally located close to the telomeres, however, they are
less useful than microsatellites for genome–wide linkage
analyses
▪ Macrosatellite: repeats are larger still and may be many mega
bases in length. They are found at the ends (telomeres) of the
chromosomal arms and in the central chromosomal
constriction (centromere). Length variation is common and
accounts for visible differences in the size of chromosomal
centromeric regions
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