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Haplogroup J1 is a prevalent Y-chromosome lineage within the Near East. We report the frequency and YSTR diversity data for its major sub-clade (J1e). The overall expansion time estimated from 453 chromosomes is 10,000 years. Moreover, the previously described J1 (DYS388=13) chromosomes, frequently found in the Caucasus and eastern Anatolian populations, were ancestral to J1e and displayed an expansion time of 9000 years. For J1e, the Zagros/Taurus mountain region displays the highest haplotype diversity, although the J1e frequency increases toward the peripheral Arabian Peninsula. The southerly pattern of decreasing expansion time estimates is consistent with the serial drift and founder effect processes. The first such migration is predicted to have occurred at the onset of the Neolithic, and accordingly J1e parallels the establishment of rain-fed agriculture and semi-nomadic herders throughout the Fertile Crescent. Subsequently, J1e lineages might have been involved in episodes of the expansion of pastoralists into arid habitats coinciding with the spread of Arabic and other Semitic-speaking populations.

Objective: Although socioeconomic status (SES) has been linked to multiple health outcomes, there have been few studies of the effect of SES on the provision of bystander cardiopulmonary resuscitation (CPR) during cardiac arrest events and no studies that we know of on the effect of SES on the provision of dispatcher-assisted bystander CPR. This study sought to define the relationship between SES and the provision of bystander CPR in an emergency medical system that includes dispatcher-provided CPR instructions., Methods: This study was a retrospective, cohort analysis of cardiac arrests due to cardiac causes occurring in private residences in King County, Washington, from January 1, 1999, to December 31, 2005. We used the tax-assessed value of the location of the cardiac arrest as an estimate of the SES of potential bystanders as well as multiple measures from 2000 Census data (education, employment, median household income, and race/ethnicity). We also examined the effect of patient and system characteristics that may affect the provision of bystander CPR. Logistic regression models were used to analyze the association of these factors with two outcomes: the provision of bystander CPR with and without dispatcher assistance., Results: Forty-four percent (1,151/2,618) of cardiac arrest victims received bystander CPR. Four hundred fifty-seven people (17.5% of the entire study population, 39.7% of those who received any bystander CPR) received CPR without telephone instructions. A total of 694 people received dispatcher-assisted bystander CPR (25.6% of the entire population, 60.4% of those receiving any bystander CPR). After adjusting for demographic and care factors, we found a strong association between the tax-assessed value of the cardiac arrest location and increased odds of the provision of bystander CPR without dispatcher instructions and bystander CPR with dispatcher assistance compared with no bystander CPR., Conclusions: This study suggests that higher bystander SES is associated with increased rates of bystander CPR with and without dispatcher instructions. CPR training programs that target lower-SES communities and assessment of these training methods may be warranted.

While not free from hazards, CT-guided biopsy of the lung is a safe procedure, with few major complications. Despite its safety record, however, potentially fatal complications do rarely occur. We report a case of pericardial tamponade following CT-guided lung biopsy. Rapid diagnosis and therapy allowed for complete patient recovery. Physicians who perform this procedure should be aware of the known complications and be prepared to treat them appropriately.

SUMO-1, a ubiquitin-like protein, is covalently bound to many proteins, leading to chromatin inactivation and transcriptional repression. The high concentration of SUMO-1 on the XY body in rodents suggests that this protein has an important role in facultative heterochromatin organization. In human, the precise role of SUMO in chromatin/heterochromatin organization remains to be defined. Here we describe the SUMO-1 distribution, during human male meiosis, in relation to the formation of the different types of heterochromatin. We show that, during late pachynema, SUMO-1 appears on the constitutive heterochromatin, but is excluded from the XY body facultative heterochromatin. At the SUMO-1 labelled areas, the presence of HP1alpha protein, as well as of trimethylated H3-K9 and H4-K20 histone modifications, supports a role for SUMO-1 in constitutive heterochromatin organization. We also establish that, on the constitutive heterochromatin, H4-K20me3 staining progressively decreases as SUMO-1 staining increases, suggesting that core histone(s), and histone H4 in particular, are direct targets for sumoylation. Our results also suggest that, in the context of global histone H4 hyperacetylation that precedes the histone-to-protamine transition at postmeiotic stages of spermatogenesis, histone H4 sumoylation may represent an important epigenetic marker replacing methylation on the constitutive heterochromatin.

A large scale factor XI (FXI) mutation screening program identified a number of novel candidate mutations and previously reported mutations and polymorphisms. Five potential missense mutations were selected for further study; these included two novel missense mutations - Met-18Ile (p.Met1Ile) and Met102Thr (p.Met120Thr), two previously reported missense mutations - Tyr133Ser (Tyr151Ser) and Thr575Met (Thr593Met), and one amino acid substitution previously reported as a polymorphism - Arg378Cys (Arg396Cys). The substitutions were recreated by the site-directed mutagenesis of a FXI cDNA and stably expressed in a BHK-570 cell line. Subsequent analysis of both the conditioned media and cell lysates showed that three of the substitutions, Met-18Ile, Met102Thr andTyr133Ser, prevented secretion of the mutated protein from the transfected cell line, resulting in a cross-reactive material negative (CRM-) phenotype. The remaining two mutants, Thr575Met and Arg378Cys, secreted significant levels of FXI into the conditioned media; however, these mutant FXIs were shown to have negligible factor IX activation activity in an APTTbased assay. These results confirmed all five of the missense mutations as being causative of factor XI deficiency, despite one having been previously reported as a polymorphism (Arg378Cys) and one (Tyr133Ser) as a mild mutation - FXI:C 38 U/dl in a homozygous patient.

Transcriptional silencing of the sex chromosomes during male meiosis (MSCI) is conserved among organisms with limited sex chromosome synapsis, including mammals. Since the 1990s the prevailing view has been that MSCI in mammals is transient, with sex chromosome reactivation occurring as cells exit meiosis. Recently, we found that any chromosome region unsynapsed during pachytene of male and female mouse meiosis is subject to transcriptional silencing (MSUC), and we hypothesized that MSCI is an inevitable consequence of this more general meiotic silencing mechanism. Here, we provide direct evidence that asynapsis does indeed drive MSCI. We also show that a substantial degree of transcriptional repression of the sex chromosomes is retained postmeiotically, and we provide evidence that this postmeiotic repression is a downstream consequence of MSCI/MSUC. While this postmeiotic repression occurs after the loss of MSUC-related proteins at the end of prophase, other histone modifications associated with transcriptional repression have by then become established.

Objective: To study the meiosis of a patient with complete azoospermia factor (AZF)b deletion of the Y chromosome., Design: Case report., Setting: La Conception University Hospital, Marseille, France., Patient(s): One azoospermic patient., Intervention(s): Yq deletion testing, testicular sperm extraction, and meiotic study with immunocytochemistry., Main Outcome Measure(s): Abnormal synapsis rates in spermatocytes., Result(s): We found that most spermatocytes were at an early stage of meiosis. Half of the meiotic germ cells analyzed showed asynapsis, which was mostly extended or total. Discontinuity in the synaptonemal complex was seen in one third of the meiotic cells analyzed. An unusually small number of normal pachytene nuclei were found, all at early pachytene substages., Conclusion(s): This is the first demonstration that the synaptic process is impaired in a man with complete deletion of the AZFb interval. Our findings provide evidence that the pachytene checkpoint is situated at the midpachytene substage in humans.

Factor VII (FVII) plays a critical role in the initiation of blood coagulation, and patients with dysfunctional or reduced levels of this protein are susceptible to mucosal bleeding. There is poor correlation between the clinical presentation and the phenotypic data; and in cases of a mild bleeding tendency, mild to moderate reductions in both FVII antigen and activity may be overlooked. The prevalence of FVII deficiency may therefore be underestimated. Polymorphic differences throughout the FVII gene are associated with variations in plasma FVII antigen and activity levels. This study highlights the significance of mild FVII deficiency, and examines the importance of seven previously published polymorphisms in such patients.

We report a family in which the normal pattern of X-linked inheritance of hemophilia B (Factor IX deficiency) is complicated by mosaicism in the proband's maternal grandfather. The proband, an infant with severe Factor IX deficiency, was initially thought to be a sporadic case. Testing of other family members identified his mother as a carrier of the disorder, and his asymptomatic maternal grandfather as having very mild FIX deficiency. The causative familial mutation was identified as a two base pair deletion (AG within codons 134-135) in the Factor IX gene. The grandfather was shown to be "heterozygous" for the deletion. Karyotype analysis confirmed him to be 46XY thereby ruling out Klinefelter syndrome. The proband's aunt, who as the daughter of a man with hemophilia is theoretically an obligate carrier, was found not to carry this familial mutation, and thus not to be a carrier of hemophilia B. The grandfather must therefore be an X chromosome somatic and germline mosaic, with consequent segregation of the affected and non-affected Factor IX genes. This observation underlines the importance of confirming carrier status even in those individuals assumed to be obligate carriers, and has implications for genetic counseling.

TSPY, a candidate gene for a factor that promotes gonadoblastoma formation (GBY), is a testis-specific multicopy gene family in the male-specific region of the human Y (MSY) chromosome. Although it was originally proposed that male-specific genes on the Y originated from a transposed copy of an autosomal gene (Lahn & Page 1999b), at least two male-specific genes (RBMY and SRY) descended from a formerly recombining X-Y identical gene pair. Here we show that a TSPY homologue with similar gene structure lies in conserved positions, close to SMCX, on the X chromosome in human (TSPX ) and mouse (Tspx). TSPX is widely expressed and subject to X inactivation. TSPX and TSPY therefore evolved from an identical gene pair on the original mammalian sex chromosomes. This supports the hypothesis that even male-specific genes on the Y chromosome may have their origin in ubiquitously expressed genes on the X. It also strengthens the case for TSPY as a candidate for GBY, since independent functional studies link TSPX to cell cycle regulation.