DNAprint Genomics (DNAG)

[thesciguy]

Frog-

Everyone wants to know the 'direct' connection and that is why they all prefer direct genotype or haplotype-based association analysis.

and

Such a direct connection between genetic cause and effect is only the result of "genotype- or haplotype-based association analyses". Admixture mapping CANNOT make such a connection.

Haplotype-based analyses are not "direct". And genotype associations are not (rarely) 100%.

Direct genotype analyses are only performed AFTER another, independent, association is discovered. These associations are based on a variety of techniques (SNPs, AIMs, etc.) The benefit in Admixture mapping is that it is based on DIRECTLY associating sections of the genome with disease, and the analyses can be performed with fewer markers (a few thousand vs. 300,000 to 1,000,000 for haplotypes).*

The nature of the entire technology is the attempt to directly connect the genetically influenced characteristics of individuals to the genetic variances that cause them.

No, the nature of the entire technology is to assign specific, coarse grain, genetic variation (markers) to the PROBABILITY of a trait (disease, drug response, etc.). Once those variations are identified, a fine-grain analysis MIGHT follow. But even this in not a "direct" association. For example, the fine-grain genetic variations realted to breast cancer is a mutation (more than 600) in the BRCA1 and BRCA2 genes. But having a mutation is not a gurantee of disease. 20% of patients with mutations in BRCA1 and BRCA2 will never develop breast cancer, and we don't know why.

Admixture mapping can only indicate a very vague probability regarding a trait and its variance.

Sometimes yes, sometimes no. It depends on the strenght of the data.

Those AIMs might be considered an alternative set of search criteria to the trait in question, until you realize that every descendant of Alpha's brother (who don't carry the variant) have exactly the same set of AIMs. Not to mention everyone else in the village/region at the time.

Bingo! This is precisely what Admixture mapping needs in order to work. In this example, the greater the similarity between the disease group and normal group (in terms of their AIMs), the better ability for Admixture to map the genetic variant of the disease.

Admixture mapping may present some interesting trends, but it does not provide the cause and effect relationships that are essential to the eventual understanding of the genome.

There is no one in my field that presumes to know WHAT will eventually lead to a greater understanding of the cause and effect relationship of the genome and disease. We are exploring everything. Admixture is more than an "interesting trend" in my opinion. It is a faster and cheaper way to quickly separate the wheat from the genomic chaff when searching for cause of genetic disease.

Frog, you can curse the darkness, or light a candle. The choice is yours.

Good Luck.


*Am J Hum Genet. 2004 May; 74(5): 979–1000.