Tag Archives: Genetics + Biology

Anticipating trouble

Science magazine today reports another ego trip.

A U.S. company [454] has begun to trickle out information on a unique DNA study it calls “Project Jim,” a crash effort to sequence the entire genome of a single individual. The results are likely to be made public this summer. Anonymity is out of the question: It has already been announced that the genome belongs to James D. Watson, winner of the Nobel Prize and co-discoverer of DNA’s structure. Watson won’t be alone: Harvard Medical School has approved a plan by computational geneticist George Church to sequence and make public the genomes of well-informed volunteers—including his own. And J. Craig Venter says his nonprofit institute will soon release a complete version of his genome.

My daily newsletter says that Roche is going to acquire 454 for $155M and plans to use the sequencer for IVD applications, I hope they will forget “Project Jim” somewhere on a harddisk.

Collins: Testimony on the threat of genetic discrimination

The testimony of Francis Collins before the subcommittee on Health is now online

A recent NIH study of families at risk for hereditary nonpolyposis colorectal cancer … revealed that the number concern expressed by participants regarding genetic testing was about losing health insurance, should the knowledge of their genetic test result be divulged or fall into the “wrong hands” … Unless Americans are convinced that their genetic information will not be used against them, the era of personlized medicine may never come to pass. The rest would be a continuation of the current one-size-fits-all medicine, ignoring the abundant scientific evidence that the genetic differences among people help explain why some of us benefit from a therapy while others do not.

Autosomal inheritance of sex-linked marker

While optimizing the analysis strategy for a 500,000 SNP Affymetrix array set, I found 6 autosomal SNPs that show highly significant sex-dependent allele differences: rs2809868, rs4862188, rs2880301, rs3883011, rs3883013 and rs3883014.


Sure, there could be autosomal marker that influences male/female outcome but there is a more likely explanation: All SNPs have paralogue sequence stretches on the Y chromosome that are co-amplified during PCR. From the initial genotyping results it is most likely that only the Y chromosomal stretch is being mutated in SNP 4, 13 and 15.2.

These SNPs are perfect sex marker, as they include an autosomal control allele (in comparison to pure Y markers like SNPs in SRY). They are always unambiguous (in contrast to pure X marker where only heterocygotes are informative).

They even offer advantage to commercial STR kits of the Amelogenin/Amely gene situated (in the Y parautosomal region) as they would not be affected by excess homologous X chromosomal material as often found in forensic situations. In addition, they might overcome some other weakness of the Amelogenin test where a second assay is usually recommended.

If you will ever see a case-control study that is highlighting any of these SNPs, you can be sure that this study had a distorted male-female ratio between case and controls.

The other way around

One of my favorite pictures is the Orangenesser by Baselitz – his speciality is to paint his subjects the other way around to free the subject from its content (this is at least what art curators say).

DNA inversion rearrangements seem to be also more frequent in the human genome as previously thought, see the following PNAS preprint:

Three such regions … on chromosomes 3, 15, and 19, were analyzed. … The results obtained indicate that recurrent genomic rearrangements occur at relatively high frequency in somatic cells. Interestingly, the rearrangements studied were significantly more abundant in adults than in newborn individuals, suggesting that such DNA rearrangements might start to appear during embryogenesis or fetal life and continue to accumulate after birth.

(more on arts and DNA)