Molecular Markers - Genetics

Genotypic Groups in Continuous Traits

Traits determined by multiple genes, each contributing a small additive effect, represented by expressions like x⁶ + x⁵y + x⁴y².

SNP (Single Nucleotide Polymorphism)

A variation in a single nucleotide occurring at a specific position in the genome, often common in a population (>1%).

SNV (Single Nucleotide Variant)

A single nucleotide change in the genome, which can be common or rare.

Types of traits useful for SNPs/SNVs

Examples include cystic fibrosis, sickle cell anemia, diabetes, cancer susceptibility, and cardiovascular disease.

Haplotype

A group of alleles or SNPs inherited together due to their physical proximity on the chromosome.

Linkage of Haplotype SNPs

Yes, haplotype SNPs are often inherited together due to their close location on the chromatid, reducing recombination chances.

Molecular Markers

Identify genetic variations associated with monogenic disorders (e.g., Huntington’s disease) and complex traits (e.g., asthma, Alzheimer’s disease).

Why are nearby SNP/SNVs inherited together?

Due to their proximity, they are tightly linked, resulting in rare recombination.

Tracking SNP/SNVs in disorders

By analyzing pedigree data and genome-wide association studies (GWAS) for correlations with specific disorders.

GWAS

Genome-Wide Association Study, which analyzes SNPs associated with specific traits or disorders.

Why scan the genome-wide for SNPs/SNVs?

Many traits are polygenic; GWAS identifies multiple genetic regions simultaneously rather than focusing on one gene.

DNA restriction enzyme function

Cuts DNA at specific recognition sites, typically palindromic sequences.

Cohesive vs. Blunt End

Cohesive ends have overhanging single-stranded DNA ends; blunt ends have no overhang with cuts at the same position.

Palindrome in restriction motif

A sequence of DNA that reads the same in the 5’ → 3’ direction, e.g., 5’-GAATTC-3’.

Recombinant DNA

DNA formed by combining sequences from different organisms; requires a vector, restriction enzymes, and ligase to clone a gene.

RFLP (Restriction Fragment Length Polymorphism)

Technique using restriction enzymes to cut DNA, revealing differences in fragment sizes due to sequence variations.

PCR (Polymerase Chain Reaction)

Amplifies specific DNA sequences; DNA bands are visualized using agarose gel and dyes.

Use of PCR with RFLP

PCR amplifies DNA, then RFLP analyzes the amplified DNA for variations in restriction sites.

Co-segregation

Inheritance of genetic markers together, often due to linkage.

Co-segregating factors in pedigree analysis

Molecular marker (e.g., SNP) and phenotype (e.g., disease trait).

Restriction enzymes and RFLPs co-segregating with diseases

Only enzymes that cut at polymorphic sites associated with diseases produce co-segregating RFLPs.

Location of molecular markers in relation to disease genes

Markers are often near the disease gene but not necessarily within it.

Types of Molecular Markers

Examples include SNPs and microsatellites (Short Tandem Repeats, STRs).

Genetic predisposition vs. predetermination

Predisposition indicates a higher likelihood of developing a condition; predetermination guarantees condition development regardless of environment.