DNA Repeat In Human Genome PDF

DNA REPEAT IN HUMAN GENOME DR. AHMED HASSAN Repetitive DNA: A Tool to Explore Animal Genomes/Transcriptomes The term “repetitive sequences” (repeats, DNA repeats, repetitive DNA) refers to DNA fragments that are present in multiple copies in the genome. Highly repetitive sequences These...

DNA REPEAT IN HUMAN GENOME DR. AHMED HASSAN Repetitive DNA: A Tool to Explore Animal Genomes/Transcriptomes The term “repetitive sequences” (repeats, DNA repeats, repetitive DNA) refers to DNA fragments that are present in multiple copies in the genome. Highly repetitive sequences These are are short sequences (5 to10 bp) amounting 10% of the genome and repeated a number of times, usually occurring as tandem repeats (present in approximately 106 copies per haploid genome). However, they are not interspersed with different non-repetitive sequences. Usually, the sequence of each repeating unit is conserved. Most of the sequences in this class are located in the heterochromatin regions of the centromeres or telomeres of the chromosomes. Highly repetitive sequences interacting with specific proteins are involved in organizing chromosome pairing during meiosis and recombination.  Satellite DNA These are represented by monomer sequences, usually less than 2000- bp long, tandemly reiterated up to 105 copies per haploid animals and located in the pericentromeric and or telomeric heterochromatic regions )  Moderately or dispersed repetitive sequences These include: (a) short (150 to 300-bp) sequences 40% of the total genome. (b)long ones (5-kbp) amounting about 1-2% of the total genome. ❑ These are dispersed throughout the euchromatin having 103 - 105 copies per haploid genome. ✓ These sequences are involved in the regulation of gene expression. ✓ In some cases, long dispersed repeats of 300 to 600-bp show homology with the retro viruses. ❑On the basis of their mode of amplification, repetitive DNA sequences may be tandemly arranged or interspersed in the genome  Interspersed repetitive DNA ❑ Interspersed repeat sequences scattered throughout the genome have arisen by transposition, having “ability to jump from one place to another in the genome”. Even though the individual units of interspersed repetitive noncoding DNA are not clustered, taken together they account for approximately 45% of the human genome. By the mechanism of their transposition, interspersed repeats are classified into two classes: (a) RNA transposons (b) DNA Transposons  (a) RNA transposons RNA transposons also known as retroelements found in eukaryotic genome require reverse transcription for their activity. ❑ Based on their structural relationship, RNA transposons are divided into two general categories: (a) LTR elements (b) Non LTR elements (a) LTR elements LTR includes retroviruses whose genomes are made up of RNA.They infect different types of vertebrates. ❑ Endogenous retroviruses (ERVs) These are retroviruses integrated into the vertebrate chromosomes and inherited from generation to generation as part of the host genome. Non LTR elements (a) LINEs (Long Interspersed Nuclear Elements) LINEs are several thousand base pairs in size and make up about 17% of the total human genome ❑ They contain reverse-transcriptase-like gene involved in retrotransposition process. ❑ no function of LINE 1 repeat is yet known. (b) SINEs (Short Interspersed Nuclear Elements) SINEs are small elements, usually 100 to 500-bp in length, accounting for 11% of the human genome ❑ SINEs do not have reverse transcriptase gene, instead they borrow reverse transcriptase enzymes from other retroelements. DNA Transposons ❑ DNA transposons do not require RNA intermediate and transpose in a direct DNA-to-DNA manner. ❑ In eukaryotes, DNA transposons are less common than retrotransposons.  Tandem repeats ❑Tandem repeats consists of repeat arrays of two to several thousand- sequence units arranged in a head to tail fashion. Tandem repeats may be further classified according to the length and copy number of the basic repeat units as well as its genomic localization. (a) Mega satellite DNA These are characterized by tandemly repeated DNA in which the repeat unit is approximately 50-400 times, producing blocks that can be hundreds of kilobases long. (b) Minisatellite DNA (variable number of tandem repeats (VNTR) This comprises tandem copies of repeats that are 6-100 nucleotides in length ❑ minisatellites are GC rich ❑ Minisatellite mutations usually consist of gains or losses of one or more repeat units. (b) Minisatellite DNA (variable number of tandem repeats (VNTR) ❑ minisatellites are clustered near sub-telomeric ends of the chromosomes (I) Telomeric repeats These are composed of multiple repeats of short sequence elements (typically 5 to 8-bp in length, with a GT-rich strand oriented 5' to 3' toward the end of the chromosome) and range in length from a few repeat units to >10-kbp. (II) Subtelomeric repeats Sub-telomeric Repeats are the classes of repetitive sequences that are interspersed within the last 500,000 bases of non-repetitive DNA located adjacent to the telomere.  (c) Microsatellite /Short Sequence Repeats (SSRs) Tandem repeats are made up of usually, di-, tri-, or tetranucleotide units (1-6 bps) ❑ Microsatellites or simple sequence repeats (SSRs) are ubiquitously interspersed in coding and non-coding regions of the eukaryotic and prokaryotic genomes ❑ All the SSRs taken together occupy about 3% of the human genome in which they are widely dispersed and associated with many genes ❑ play significant roles in regulation of gene expression by forming various DNA secondary structures and offering a mechanism of unwinding  S H O RT TA N D E M R E P E AT S ( S T R S ) O R (SSRs) M I C R O S AT E L L I T E S  MICROSATELLITES Microsatellites are widely used for DNA profiling, also known as "genetic fingerprinting", of crime stains (in forensics) and of tissues (in transplant patients). They are also widely used in kinship analysis (most commonly in paternity testing)  What are microsatellite markers? Microsatellite markers, or short tandem repeats (STR), are polymorphic DNA loci containing repeated nucleotide sequences, typically from 2 to 7 nucleotides per unit.  How are short tandem repeats used in DNA profiling? The system of DNA profiling used today is based on PCR and uses simple sequences or short tandem repeats (STR).... These STR loci (locations on a chromosome) are targeted with sequence-specific primers and amplified using PCR. The DNA fragments that result are then separated and detected using electrophoresis.  What is a microsatellite locus and why are they frequently used in population genetics? Microsatellite markers are inherited from both parents, making them useful for parentage analysis (think paternity testing) and population genetic studies.... If a microsatellite locus is polymorphic, it means that there is more than one potential allele at a single locus (a specific marker site).  What is involved in DNA profiling? DNA profiling is a forensic technique in criminal investigations, comparing criminal suspects' profiles to DNA evidence so as to assess the likelihood of their involvement in the crime. It is also used in parentage testing, to establish immigration eligibility, and in genealogical and medical research. What are short tandem repeats and why are they important? Short tandem repeats (STRs) are short tandemly repeated DNA sequences that involve a repetitive unit of 1–6 bp. Because of their polymorphisms and high mutation rates, STRs are widely used in biological research