5.5
Polimorfismi a singolo nucleotide - SNP
Un polimorfismo a singolo nucleotide o SNP è una variazione di singolo nucleotide in una specifica posizione genomica in una vasta popolazione. È il t…
Quando si confrontano più genomi umani, si osservano variazioni nelle sequenze.
Le variazioni dovute alla sostituzione di un nucleotide sono chiamate polimorfismi a singolo nucleotide o SNP.
Le variazioni dovute all'inserimento o alla delezione di una sequenza di nucleotidi di lunghezza inferiore a un kilobase sono chiamate indel.
Se un'inserzione o una delezione di nucleotidi viene copiata un numero variabile di volte nello stesso genoma, si parla di variazione del numero di copie o CNV. Spesso, le CNV coinvolgono grandi tratti di DNA di lunghezza superiore a un chilometro.
Un aplotipo è un insieme di geni ereditati da un singolo genitore. Un genoma può essere diviso in blocchi di aplotipi che contengono gruppi di polimorfismi.
Poiché si verificano pochi incroci tra cromosomi omologhi durante ogni meiosi, i blocchi di aplotipi sono stati ereditati in un gruppo collegato attraverso le generazioni.
View the full transcript and gain access to JoVE Core videos
Q1: What is a single nucleotide polymorphism and how common are SNPs in the human genome?
A single nucleotide polymorphism (SNP) is a variation where one nucleotide differs at a specific genomic position. SNPs are the most prevalent type of sequence variation in humans, occurring approximately once every 1,000 nucleotides. Point mutations present in more than 1% of the population qualify as SNPs, making them valuable markers for genetic research and disease association studies.
Q2: What is the difference between transitions and transversions in SNPs?
Transitions involve substituting one purine with another purine (A/G) or one pyrimidine with another pyrimidine (C/T). Transversions replace a purine with a pyrimidine or vice versa (A or G with C or T). In SNPs, transitions occur more frequently than transversions, making them a more common type of nucleotide substitution observed across populations.
Q3: How do SNPs differ from indels and copy number variations?
SNPs involve substitution of a single nucleotide, while indels are insertions or deletions of nucleotide sequences less than one kilobase in length. Copy number variations (CNVs) occur when insertions or deletions are repeated multiple times in the same genome, often involving DNA stretches greater than one kilobase. Each variation type represents distinct mechanisms of genetic diversity in human populations.
Q4: What are haplotype blocks and why do they persist across generations?
Haplotype blocks are clusters of polymorphisms inherited together from a single parent as a linked group. Few crossovers occur between homologous chromosomes during meiosis, allowing these blocks to remain intact and be inherited together across generations. This linkage makes haplotype blocks useful for tracking genetic variation and identifying disease-associated regions in genome-wide association studies genetic variations and diseases.
Q5: Where are most SNPs located in the genome and what is their significance?
Most SNPs are found in introns, non-coding regions that do not produce proteins. These intronic SNPs serve as biological markers to locate genes associated with particular diseases. However, SNPs within genes or regulatory sequences near genes may directly affect gene function and cause disease, making their location critical for understanding phenotypic consequences.
Q6: Why are SNPs preferred over short tandem repeats for genotyping studies?
SNPs are more abundant and stable than short tandem repeats (STRs), which involve di-, tri-, or tetranucleotide repeats. Additionally, some SNPs directly affect the phenotype, providing functional relevance beyond simple genetic markers. These advantages make SNPs the preferred choice for genotyping and identifying genetic variations in large-scale population studies.
Q7: How can SNPs be used to identify disease-associated genes?
SNPs serve as biological markers that help locate genes linked to specific diseases. When SNPs are present in introns or regulatory sequences, they can be tracked across populations to identify disease associations. SNPs that fall within genes or affect regulatory regions may directly influence gene expression and disease susceptibility, enabling researchers to map disease-causing variants.