(Image courtesy of CIMA http://www.cima.es/areas1_neuro/areas1_neuro_english.html) 

Data from one of the first genome-wide association studies (GWAS), which focused on Parkinson’s diseases and was funded in part by The Michael J. Fox Foundation for Parkinson’s Research (MJFF), is now being made available to researchers through the National Human Genome Research Institute (NHGRI) and the National Center for Biotechnology Information (NCBI), both of the National Institutes of Health (NIH). NHGRI hopes to speed up research by making previously unavailable GWAS data sets publicly available to the research community.

The study, conducted by researchers at Mayo Clinic in Rochester, Minn., in collaboration with scientists at Perlegen Sciences, Inc., in Mountain View, Calif., was the first genome-wide association study applied to Parkinson’s disease. It was funded under MJFF’s Linked Efforts to Accelerate Parkinson’s Solutions (LEAPS) initiative.

“The Michael J. Fox Foundation is committed to spurring innovation by creating every possible opportunity for researchers to collaborate and share their knowledge,” said Katie Hood, chief executive officer of The Michael J. Fox Foundation.

Researchers interested in accessing the Mayo-Perlegen LEAPS Collaboration study dataset should go to dbGaP’s Web site and complete a request for access to the individual-level data at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000048. Information on data access request procedures is available through the dbGaP “controlled access” Web page, at http://dbgap.ncbi.nlm.nih.gov/aa/wga.cgi?login=&page=login.

Elaine Warburton  www.geneticsandhealth.com

Papers published in Nature and Science this week support the previously held theory that humans originated in East Africa, migrating outward until they reached all parts of the globe. But the genetic work from these studies brings a new level of precision to human migration studies, with each group finding subtle and intriguing details that shed light on different aspects of human genetic variation and ancestry.

Study 1 - University of Michigan:This study was based on the analysis of more than 500,000 SNPs and nearly 400 copy number variants — sections of DNA that are repeated or duplicated in the genome — for 485 individuals. These samples, representing individuals from 29 different populations around the world, were obtained as part of the Human Genome Diversity Project.

The results suggest East Africans are the most genetically diverse, while Native American genomes exhibit the lowest genetic diversity. Middle Eastern, Asian, and European populations, on the other hand, fall somewhere in between.  By following this decline in diversity, the Michigan team was able to retrace global human migration patterns. Consistent with previous archaeological date, language studies, and smaller genetic studies of mitochondrial DNA or autosomal or sex chromosomes, the research suggests humans originated in Africa, migrating first to the Middle East, then to Europe, Asia, the Pacific Islands, and — eventually — the Americas.

Study 2 - Cornell University: This study used comparative genomics to analyze 39,440 autosomal SNPs in 10,150 sequences from 15 African-Americans and 20 European-Americans.  Using the PolyPhen computer algorithm, they also assessed how many of the nucleic acid changes in each population were likely to produce amino acid changes that were “possibly” or “probably” damaging.

The researchers observed that the overall genetic diversity was higher in those of African descent, they found that those of European descent had more genetic variations that were predicted to be damaging. The authors attribute this to differences in population age and suggest European populations may have undergone a more recent population bottleneck — a decrease in population that leads to the selection of certain genetic traits — than their African ancestors.

Study 3 - Stanford Human Genome Center: This large study assessed 642,690 SNPs from 938 individuals from 51 populations and measured the genetic variation at each of the loci  and provided valuable information into human genetic variation both on a global scale as well as within relatively small geographic areas.

Specifically, the study found evidence for decreasing haplotype heterozygosity in populations as they moved further and further away from Addis Ababa, Ethiopia.  The study also found genetic evidence for differences in ancestry within populations. For instance, some individuals from the Middle East, such as Palestinians, Druze, and Bedouins, had ancestors from the Middle East as well as Europe and parts of South and Central Asia.

The results of these studies, while intriguing from a human ancestry perspective, may also provide insights into interpreting the genetics of some diseases, since they provide a framework for understanding genetic variation.

Elaine Warburton  www.geneticsandhealth.com
 

Our early human ancestors originated from a hot, humid climate where natural selection focused on dispersing heat.  As humans migrated to colder climates there would have been evolutionary pressure to adapt to their new settings by boosting the processes that produce and retain heat.

Genes involved in energy metabolism are therefore likely to be central to heat and cold tolerance. 

Researchers from the Dept of Human Genetics, University of Chicago, USA tested this theory by genotyping 873 tag SNPs in these ‘cold tolerance’ genes in 54 worldwide populations and found a correlation with climatic variations.

Among the results were strongest signals from several SNPs, that had previously been associated with body evolution directly related to cold tolerance.

One, a leptin receptor,  LEPR R109K, which is integral in appetite regulation and energy balance, was the source of one of the strongest signals of evolutionary selection. One version of this gene is common in locations with colder winters. This allele is additionally correlated with the increased capability to absorb oxygen and expel carbon dioxide, which happens when the body produces heat. The same genetic variation has also been linked to a lower BMI, a smaller amount of abdominal fat, and a lower blood pressure. This specific leptin receptor, therefore, is protective against metabolic syndrome.

However, not all of the genes related to tolerance of colder climates protects against the metabolic syndrome. For example, an increased blood glucose level might protect the body from cold weather by making energy more readily available for production of heat. However, this also raises the risk of type 2 diabetes. FABP2 A54T was a gene that was more prevalent in populations with lower temperatures actually increases BMA, promotes storage of fat in the body and increases levels of cholesterol. While this protects the body against the cold, it increases the risk of heart disease and diabetes, and thus metabolic syndrome.

Variation in climate may be correlated with other aspects of environmental variation. Nevertheless, the results are consistent with the idea that climate has been an important selective pressure acting on candidate genes for common metabolic disorders such as obesity, diabetes and heart disease.

Thousands of years later we live in an era that combines widespread central heating with an overabundant food supply, so those genetic alterations which protected us from cold have taken on a different sort of significance. They alter our susceptibility to a whole new set of diseases, such as obesity, coronary artery disease and type 2 diabetes.

For further information, please click on:

http://genetics.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pgen.0040032&ct=1

Elaine Warburton  www.geneticsandhealth.com