Gene polymorphism,structure and ffunction..

1. Gene structure and function
By
Ahmad Saad Almenshawy
Assistant Lecturer of Clinical Pathology
Faculty of Medicine, Mansoura University

2. What is gene?!
• It is a specific DNA sequence that encodes for
a specific protein.
• During gene expression, it is transcripted into
mRNA which is translated into a specific
protein.

3. Molecular Basis

4. Gene structure
• Although the gene is consisted of many
elements, the coding part is represented in a
small region.
• Some regions are not translated and others
not even transcripted.

5. • Promoter is a region of DNA that initiate
transcription of specific gene . It is located
near the transcription site of genes, on the
same strand and up stream on the DNA. It can
be about 100-1000 base pairs long.
• Transcription factors (TF) are proteins that
bind to DNA alone or with other proteins to
regulate gene expression by promoting or
suppressing transcription.

6. • Activator is a protein that increases
transcription of gene or set of genes. Most
activators are DNA binding proteins that bind
to enhancers.
• Repressor is a DNA or RNA binding protein
that inhibits the expression of one or more
genes by binding the silencers.

7. • Enhancer is a short (50-1500bp) region of
DNA that can be bound by proteins
(activators) to increase the likelihood that
transcription of particular gene will occur.
• Silencer is a DNA sequence capable of binding
repressors. When a repressor protein binds to
silencer region of DNA, RNA polymerase is
prevented from transcripting the DNA sequence
into RNA.

8. From a gene into complete chromosome

9. Gene Function
• Gene expression is the process by which gene
code is transformed into functional gene
products. These products are often proteins,
but in non protein coding genes such as tRNA
genes, the product is functional RNA.

10. • Genetic code is a set of three nucleotides
Known as codons, each correspond to specific
amino acid.
• In addition ,a “start codon“ and three "stop
codon“ indicate the beginning and end of the
protein coding region. There are 64 possible
codons and only 20 standard amino acids;
hence the code is redundant and multiple
codons specify the same amino acids. The
correspondence between codons and amino
acids is nearly universal among all known
living organisms.

11. Gene function

13. Mutations and polymorphism
• When a variant is so common that it
represents more than 1% of chromosomes in
general population , so it is known as genetic
polymorphism.
• Usually the mutation results in harmful effects
while polymorphism results in variation in
protein products.

14. Classification of mutations:
• Small scale mutation:
Insertions means add one or more extra
nucleotides into the DNA.
Deletions means removal one or more
nucleotides from the DNA.
Substitution mutations means exchange a single
nucleotide for another. It results in to
synonymous or non synonymous which sub
classified into non sense or mis sense mutations.

15. • Large scale mutation:
Amplifications or duplications which lead to
multiple copies of all chromosomal regions.
Deletions of large chromosomal regions
leading to loss of the genes within those
regions.
Large scale changes to the scale of
chromosomes which includes chromosomal
translocations and inversions.
Loss of heterogeneity.

16. Classification according effect on
function:
• Loss of function mutation.
• Gain of function mutation.
• Dominant negative mutation.
• Hypomorphs.
• Neomorphs.
• Lethal muations.

17. Systems used for nomenclature:
• Human genome variation society (HGVS).
• Human genome organization (HUGO); it uses
HUGO gene nomenclature committee to give
names for new mutations or polymorphisms.
• Online mendelian inheritance of man (OMIM).

18. Sequence variation nomenclature
• "c." for a coding DNA sequence (like c.76A>T).
• "g." for a genomic sequence (like g.476A>T).
• "m." for a mitochondrial sequence (like
m.8993T>C).
• "r." for an RNA sequence (like r.76a>u).
• "p." for a protein sequence (like p.Lys76Asn)

21. Types of gene polymorphism:
• Single nucleotide polymorphisms (SNPs):
they are a single nucleotide changes that happen
in the genome in a particular location. It is the
most common form of genetic variation.
• Small-scale insertions/deletions (Indels):
consist of insertions or deletions of bases in
DNA.
• Microsatellites:
they are repeats of 1-6 base pairs of DNA
sequence. Microsatellites are commonly used as
a molecular markers especially for identifying
the relationship between alleles.

22. What is genetic linkage ?
• It is the tendency of DNA sequences that are
close together on a chromosome to be
inherited together during the meiosis phase of
sexual reproduction. On another word, two
genetic markers are physically near to each
other and unlikely to be separated onto
different chromatids during chromosomal
crossover and therefore said to be more
linked.

23. Linkage disequilibrium
• It is non random association of alleles at
different loci in a given population. Loci are
said to be in linkage disequilibrium when the
frequency of association of their different
alleles is higher or lower than what would be
expected if the loci were independent and
associated randomly alleles.

24. Methods of gene polymorphism
detection:
1. PCR-RFLP.
2. Multiplex PCR.
3. Allele specific amplification.
4. TaqMan real-time PCR.
5. Oligonucleotide ligation assay.
6. High density chip array technology.
7. Mass spectrometry.
8. Next generation sequencing (NGS)

25. Restriction fragment length polymorphism (RFLP)