Volume 42 Issue 9, September 2010

Two genome-wide association studies for meningococcal disease and tuberculosis identify new loci associated with susceptibility to these infectious diseases. They highlight a role for the acquired and innate immune systems in host control of several human pathogens and demonstrate that denser genotyping platforms and population-specific reference panels are necessary for genetic studies in African populations.

The transition from fetal to adult β-like globin expression is a key step in the maturation of the red blood cell lineage. Two new studies show that the KLF1 zinc finger protein uses direct and indirect means to regulate the final switch from fetal to adult globin expression and that monoallelic loss of KLF1 expression leads to persistence of fetal hemoglobin.

What is the best way to identify regulatory DNA sequences such as enhancers, promoters, insulators and silencers? A new study shows that specific binding by a coactivator protein identifies enhancers that are invisible to common detection methods based on evolutionary constraint.

Adrian Hill and colleagues report a genome-wide association study for tuberculosis in cohorts from Ghana and The Gambia. They identify a host susceptibility loci for pulmonary tuberculosis disease at 18q11.2.

Tim Townes and colleagues show that knockdown of KLF1 in human and mouse adult erythroid progenitors results in reduced BCL11A levels and increased fetal hemoglobin expression. These findings suggest a potential strategy to activate fetal hemoglobin expression in individuals with β-thalassemia or sickle cell disease.

Evan Eichler and colleagues identify a large, complex structural polymorphism at 16p12.1 in a region previously associated with neurocognitive disease. They further show that the region has experienced dynamic structural evolution in primates and that disease-associated microdeletions arise on the more common human haplotype.

Hidewaki Nakagawa and colleagues report a genome-wide association study for prostate cancer in a Japanese population. They replicate previously associated loci and identify five new susceptibility loci.

Gangqiao Zhou and colleagues report a genome-wide association study for hepatocellular carcinoma in chronic hepatitis B virus carriers, identifying a new susceptibility locus at chromosome 1p36.22.

Li Dong Wang and colleagues report a genome wide association study for esophageal squamous cell carcinoma in the Chinese population. They identify two risk loci at PLCE1 and C20orf54.

Christian Abnet and colleagues report genome-wide association studies for gastric adenocarcinoma and esophageal squamous cell carcinoma in a Chinese population. They identified a new shared risk locus in the PLCE1 gene at 10q23.

Yusuke Nakamura and colleagues report a genome-wide association study of keloid, a dermal fibroproliferative growth, in the Japanese population. Their work identifies common variants at four loci associated with susceptibility to keloid formation.

Sonia Davila and colleagues report a genome-wide association study for meningococcal disease. They identify variants in the CFH region associated with susceptibility to meningococcal disease.

Lennart Hammarström, Tim Behrens and colleagues report the results of a genome wide association study of selective immunoglobulin A deficiency, the most common form of primary immunodeficiency in humans. They validated previously known HLA haplotype associations and identified a new risk variant in IFIH1.

Haydeh Payami and colleagues report results of a genome-wide association study for Parkinson's disease. They identify common variants in the HLA region associated with the late-onset sporadic form of the disease and replicate published associations with SNCA, MAPT and GAK.

Mehdi Tafti and colleagues identify new HLA class II haplotypes that are strongly protective against narcolepsy. Their analyses suggest a virtually causal role for the HLA region in determining narcolepsy susceptibility.

Jay Shendure and colleagues report exome sequencing of ten individuals with Kabuki syndrome. They identify mutations in MLL2, encoding a Trithorax-group histone methyltransferase, as causal for this rare autosomal dominant malformation disorder.

Charlotte Niemeyer, Mignon Loh and colleagues report that germline mutations at CBL are associated with developmental abnormalities and predispose individuals to juvenile myelomonocytic leukemia.

Sjaak Philipsen and colleagues report that haploinsufficiency for KLF1 causes hereditary persistence of fetal hemoglobin in a large Maltese family. They further show that KLF1 is a key activator of BCL11A, which suppresses the expression of fetal hemoglobin.

Len Pennacchio and colleagues used ChIP-Seq with the enhancer-associated protein p300 to identify 3,000 candidate cardiac transcriptional enhancers in embryonic mice at E11.5. Notably, most candidate heart enhancers at this time point are not deeply evolutionarily conserved.