5.5
Polymorphismes nucléotidiques uniques-SNP
Un polymorphisme nucléotidique unique ou SNP est une variation d'un seul nucléotide à une position génomique spécifique dans une grande population. Il…
Lorsque plusieurs génomes humains sont comparés, des variations sont observées dans les séquences.
Les variations dues à la substitution d’un nucléotide sont appelées polymorphismes mononucléotidiques, ou SNP.
Les variations dues à l’insertion ou à la suppression d’une séquence de nucléotides de moins d’un kilobase de longueur sont appelées indel.
Si une insertion ou une délétion de nucléotides est copiée un nombre variable de fois dans le même génome, on parle de variation du nombre de copies ou CNV. Souvent, les CNV impliquent de grandes étendues d’ADN de plus d’un kilobase.
Un haplotype est un ensemble de gènes hérités d’un seul parent. Un génome peut être divisé en blocs d’haplotypes qui contiennent des grappes de polymorphismes.
Étant donné que peu de croisements se produisent entre les chromosomes homologues au cours de chaque méiose, les blocs d’haplotypes ont été hérités dans un groupe lié à travers les générations.
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.