Wednesday, November 16, 2011
Sunday, November 13, 2011
This is a really cool article about the genetics of longevity from the New York Times. Its not super sciency but its a pretty good read. The genetic part of it is that there are genes that prevent major diseases (cardiovascular, cancer, diabetes, and cognitive decline) and there are the telomeres that give you a yardstick for life expectancy.
Monday, November 7, 2011
Here is some science behind the disease, Osteogenesis imperfecta. OI manifests in a number of symptoms including weak bones, multiple fractures, bowed limbs, short stature, deafness, and short lifespan. An article last week in Molecular Therapy describes the genetic basis of OI - dominant mutations in the type I collagen genes - and a new attempt at treatment through gene therapy.
Or for a more dramatic portrayal of the disease, see Bruce Willis in 'Unbreakable'.
Because of technological advances, GWAS have begun to make progress in AD genetics. A small proportion of AD patients have an autosomal dominant pattern of inheritance, and genetic studies of these patients can potentially help with patient care. Four genes, APOE, CLU, PICALM, and CR1 have been found to be involved in AD susceptibility. These genes play a role in the pathophysiology of AD, and their discovery "supports ongoing efforts towards intervention in these pathways."
Posted by Dara Dickson at 11:05 AM
ICHG/ASHG 2011: New research on genetic factors associated with autism, schizophrenia and Parkinson's
The article discussed a recent gathering of scientists in Montreal for the 12th International Congress of Human Genetics (ICHG). The focus of the gathering was to present research on certain diseases and disorders--mostly mental issues--based on genetic research. Although the researchers did not understand the genetic basis for the diseases completely, the researchers were able to get some answers out of their research and were able to make sense of some very complex things. I'm sure that the next conference will have advanced the understanding even more since the research provided great insight into understanding autism, schizophrenia, intellectual disability, epilepsy and Parkinson's diseases. A brief summary of each of the researchers findings can be found at the bottom of the article.
Sunday, November 6, 2011
This Nature article found a genetic basis for systemic lupus erythematosus. Using whole genome methylation analysis, it found hypomethylation on the IL10 and IL1R2 promoters was associated with gene activity, resulting in misregulated activity of T and B-cells. It also mentions several genes on the HLA region that carry risk factors for the lupus.
Assisted Reproductive Technologies (ART) use has increased exponentially since the first successful report came in 1978. However, it has been suggested that these methods put the babies at higher risk for genomic imprinting disorders. Specifically, Angelman's syndrome and Beckwith-Wiedemann syndrome (imprinting disorder on Ch11)have been the most studied. While these and other imprinting disorders have been shown in some studies to be more prevalent among ART kiddos, in the way of science others have failed to show such results. Global hypomethylation of maternal alleles leads credence to this idea, but small sample sizes and an inability to control for confounding variables muddles up the picture. Ah, we say it again: more science is needed to further elucidate what's really going on. In any case, this brings another moral question to the table. How does everyone feel about ART (from a medical vs. an evolutionary perspective)?
This study published today in Nature Genetics details the investigation of multiple networks of genes involved in driving colorectal cancer. Researchers profiled a vast number of genes related to the disease using the "Sleeping Beauty transposon system." Since APC mutations are widely believed to play a role in initiating colorectal cancer in humans, Sleeping Beauty was used to perform insertional mutagenesis in mice with Apc mutations. By identifying common insertion sites of Sleeping Beauty from a total of 446 excised tumors, hundreds of genes and 38 genetic networks were implicated as candidates for driving tumorigenesis.
The first genome-wide association study for dengue shock syndrome (DSS) identified SNPs at two loci, MICB and PLCE1, associated with this disease. Previous epidemiological studies found that some groups of people are more susceptible to dengue shock syndrome, possibly pointing to a genetic influence. This study compared the genomes of 2,008 pediatric cases of DSS against 2,018 control genomes in Vietnam. Another GWAS study was performed after the first with 1,737 DSS patients against 2,934 controls in order to validate their results. Two loci, MICB and PLCE1, were found to be associated with DSS patients as opposed to the controls, which suggests that dengue susceptibility might be influenced by genetic factors.
Saturday, November 5, 2011
Like in the cases of Prader-Willi Syndrome and Angelman Syndrome which are both based upon changes in the same locus, it appears that there are many instances of single genes that are implicated in multiple psychological disorders. Last year, the Gene to Cognition project finished their search for proteins involved in the postsynaptic density (the PSD: a molecular machinery involved in synaptic development and function), resulting in a list of 1461 genes, many of which are already associated with psychological disorders. Specifically, 130 diseases are now known to be linked to proteins critical to the PSD, and many of those proteins have been shown to play a role in multiple diseases. With this list of genes and proteins, it will now be possible for scientists to begin designing better therapies for disease, and perhaps creating therapies that may function in multiple diseases with similar genetic bases. It will be interesting to see how many of these disorders seem to be caused by deletions and epigenetic factors like those seen in the readings for this week and how many can be understood by more classical, Mendelian inheritance patterns.
Thursday, November 3, 2011
This study looked at the genetics of inflammatory bowel disease (IBD) which arises from an excessive inflammatory response to microbes in the bowel. Healthy food metabolism depends on the co-evolution of the bacteria inhabiting our guts and our immune system; when these two fall out of since, our immune systems attack these helpful bacteria. Using GWAS, 99 different genetic risk loci (28 of which are similar to Crohn's disease) indicating the two arise from problems in the same pathway. The two forms of IBD, childhood-onset and adult-onset, seem to have similar genetic origins, implying other genetic, environmental, and epigenetic contributions to the disease. In addition, there is a weaker association between monozygotic twins having IBD than Crohn's disease (10-15% vs 30-35%). Some of the genes suspected to be involved in both Crohn's disease and IBD are those responsible for barrier function, microbial defense, innate immune regulation, regulation of adaptive immunity, ER stress and metabolism. The frequency of different variants of the disease varies in different populations indicating selective pressures of different environments. This study highlights the proteins involved in the digestive pathway, in addition showing promise for early disease diagnosis and treatment.
Two new studies published yesterday in Nature together suggest that anatomically modern humans may have reached Europe a few thousand years earlier than previously thought. While examples of Aurignacian culture had helped us arrive at a date of approximately 43-42 kyBP for the arrival of AMHs in Europe, physical human evidence dated only to 41 kyBP at the earliest. One study reanalyzed two molars found in Italy in 1964. The molars had long been described as Neanderthal, but have only now been shown to be human through "two independent morphometric methods based on microtomographic data." The molars were dated to 45-43 kyBP. The other study revisited a maxilla, KC4, discovered in a British cave in 1927. Originally underestimated to 36-34 kyBP, researchers dated KC4 to 44.2-41.5 kyBP. The molars and KC4 now represent the oldest evidence of AMHs in all of Europe and in northwestern Europe, respectively. These findings suggest a rapid expansion of humans into Europe before the disappearance of the Neanderthals, adding fuel to the fire of the human-Neanderthal admixture debate.
This is a really interesting article about the "sixth nucleotide" which was discovered about 2 years ago. Related to 5-methylcytosine (5-mc), 5-hydroxymethylcytosine (5-hmc) may have a different function in epigenetics as compared to it's derivative; specifically, it's been implicated in DNA methylation plasticity.
This study, coming out of Emory University, quantified 5-hmc in the brain (it's enriched compared to other tissues - at around 40%) and mapped 5-hmc genome-wide in mouse cerebellum and hippocampus cells from postnatal development through adulthood. 5-hmc seems to be enriched on active genes (in contrast to 5-mc), and regions controlled by 5-hmc revealed both stable and dynamically modified loci during the period of development and aging. The team is now focusing on mapping how 5-hmc changes during development and its relationship to neurological disorders such as Rett syndrome and autism.
You can read the synopsis on Science Daily.
Researchers from Uppsala University have found evidence for genetic affinity between South East Asians and Denisovans. Instead of comparing whole genomes, they utilized genotype data for many populations and ran a sophisticated model to assess how ascertainment bias (i.e. rare SNPs not being included) could affect signals of archaic admixture. Their study included more than 1,500 samples from geographically disparate regions. Their results indicated genetic admixture among East Asians, and higher genetic affinity between Denisovans and Oceanians (previously known) as well as South East Asians.
Tuesday, November 1, 2011
This paper is a review of some of the leading hypothesis for why mental disorders are present in high numbers in populations and have not been selected against. Uher focuses specifically on fitness reducing illnesses, such as schizophrenia, autism, anorexia nervosa and biopolar disorder, among others. The persistence of these diseases is a paradox in that fitness reducing genetic variants should be under strong negative selection, however studies have shown that these diseases are highly heritable. Uher concludes that a model of polygenic mutation-selection balance best explains this paradox. Because human mental health and brain function is controlled by a large number of genes and processes, and most mutations that contribute to mental illness are newly arising, environmental factors and the cumulative effects of mildly pleiotropic genes could be responsible. It should be noted that Uher does not entertain any epigenetic contributions to mental disease in this review.