Volume 43 Issue 1, January 2011

Adult stem cells play pivotal roles in self-renewing tissues but also in the post-injury repair of adult organs that normally show little proliferative activity. A new study shows that Sox9 marks a putative adult stem cell population that contributes to the self-renewal and repair of the liver, exocrine pancreas and intestine, three organs of endodermal origin.

Genetic mapping studies in dogs, mice, zebrafish and humans have identified two new genes required for the assembly of motile cilia. The resulting gene products, CCDC39 and CCDC40, may represent previously unidentified components of the dynein regulatory complex.

To understand transcriptional regulation, it is necessary to understand the factors that determine where a particular transcription factor binds in the genome. A new study demonstrates that a single protein, FoxA1, can dictate the global DNA binding profile and the transcriptional function of estrogen receptor a in breast cancer cells and in other cell types.

Tom Karlsen and colleagues report a genome-wide association study for primary sclerosing cholangitis, a chronic bile duct disease. They identify susceptibility loci at MST1 and near BCL2L11.

Johannes Dauwerse and colleagues report the identification of mutations in the genes encoding subunits of RNA polymerases I and III, which are involved in transcription of rRNA and tRNA, in individuals with Treacher Collins syndrome. These findings support the hypothesis that TCS is a ribosomopathy.

Bernd Wollnik and colleagues report mutations in CEP152 cause Seckel syndrome, which is characterized by short stature, severe microcephaly and mental retardation. The work suggests that CEP152 has a function in genome maintenance.

Jason Carroll and colleagues report that the forkhead protein FOXA1 is an important determinant of estrogen receptor binding and show that expression of FOXA1 in non–breast cancer cells is sufficient to confer estrogen receptor binding and response to endocrine treatment.

Yoshiya Kawaguchi and colleagues show that a Sox9-positive progenitor pool located in the epithelia of the biliary and pancreatic ducts of adult mice serves as a continuous source of intestinal cells, hepatocytes and pancreatic acinar cells, identifying a shared pathway underlying the cellular renewal of these adult endodermal organs.

Michel Georges and colleagues perform high-throughput resequencing of 63 positional candidate genes identified through genome-wide association studies to search for rare coding variants influencing risk of Crohn's disease. They identify low-frequency coding variants in IL23R that confer protection against inflammatory bowel disease but conclude that rare coding variants in these positional candidates do not make a large contribution to Crohn's disease risk.

Loes van der Zanden and colleagues report results of a genome-wide association study of hypospadias, a common congenital malformation of the male external genitalia. They show that variants in DGKK on the X chromosome are associated with substantially elevated risk of this disorder.

Krina Zondervan and colleagues report a genome-wide association study for endometriosis. The authors identify a susceptibility locus on chromosome 7p15.

Zi-Jiang Chen and Yongyong Shi report a genome-wide association study for polycystic ovary syndrome, a common metabolic and endocrine disorder in women. They identified three susceptibility loci associated with this condition.

Paul Brennan, Stephen Chanock and colleagues performed a genome-wide association study for renal carcinoma. They identified two genetic susceptibility loci.

Emmanuel Mignot and colleagues report genome-wide association analyses identifying a new susceptibility locus for narcolepsy. They identify associated variants in the 3′ untranslated region of P2RY11, a purinergic receptor that modulates immune cell viability.

Michel Georges and colleagues identify a founder mutation in CCDC39 associated with primary ciliary dyskinesia in Old English Sheepdogs. They further show that mutations in human CCDC39 cause a similar phenotype and that CCDC39 is required for the assembly of inner dynein arms and the dynein regulatory complex.

Rebecca Burdine and colleagues show that CCDC40 is required for motile cilia function and correct left-right patterning in mouse, zebrafish and humans. Their findings highlight an essential role for CCDC40 in the assembly of inner dynein arms and dynein regulatory complexes.