A renaissance of "biochemical genetics"? SNPs, haplotypes, function, and complex diseases

Area of Science:

• Genetics
• Biochemistry
• Genomics

Background:

• Significant progress has been made in understanding Mendelian diseases at the molecular level.
• Current research on complex diseases relies on linkage or candidate gene approaches, often employing case/control designs.
• A deep understanding of single nucleotide polymorphism (SNP) and haplotype function is essential for these complex disease studies.

Purpose of the Study:

• To emphasize the critical importance of understanding SNP and haplotype function in complex disease research.
• To propose a vigorous advancement in the functional characterization of SNPs and haplotypes for genes with defined assayable phenotypes.
• To highlight the potential for a renaissance in biochemical genetics within the genomic era.

Main Methods:

• Utilizing functionally neutral SNPs and haplotypes for linkage studies.
• Employing functionally relevant SNPs and haplotypes for candidate gene approaches.
• Systematic investigations integrating classical biochemistry, modern genetics, genomics, and emerging technologies like microarrays.

Main Results:

• Functionally neutral variants are suitable for linkage studies, while relevant variants are best for candidate gene approaches.
• Functional characterization of SNPs and haplotypes is proposed as a key area for future research.
• The integration of diverse scientific disciplines and technologies will be instrumental.

Conclusions:

• A thorough understanding of SNP and haplotype function is vital for unraveling the genetic basis of complex diseases.
• A renaissance in biochemical genetics, incorporating modern genomic techniques, is predicted to significantly advance complex disease research.
• Systematic functional characterization of genetic variants in genes with assayable phenotypes is a promising direction.