No abstract

Druze individuals rarely marry outside their faith (often practicing consanguinity) and are thus believed to form a genetic isolate. To comprehensively characterize the genetic structure of the Druze population, we recruited and genotyped 40 parent-offspring trios from the Upper Galilee in Israel and the Golan Heights, attempting to capture different extended families (clans) across various geographical locations. Principal component (PC) and ADMIXTURE analyses demonstrated that Druze are close to, yet distinct from, other Middle-Eastern groups (Bedouins and Palestinians), supporting the Druze's Middle-Eastern origin and their recent genetic isolation. Reconstruction of the Druze demographic history using identical-by-descent (IBD) segments suggested an ≈15-fold reduction in population size taking place ≈22-47 generations ago, close to the documented time of the foundation of the Druze faith at the 11th century. Combining the Galilee and Golan Druze genotypes with previously published data on Druze from the Carmel (Israel) and Lebanon demonstrated that all four Druze communities are genetically distinct. The Lebanese group shared less IBD segments (within the group and with other groups) compared with the Israeli Druze and showed higher heterozygosity (suggesting less consanguinity), but was less diverse in PC space. These findings suggest complex recent and ancient demographic history of the Druze population.

RNA was isolated from two strains of Marek's disease virus (MDV-Z and MDV-B). The virus was grown in duck embryo fibroblasts (DEF) for 96 hr, 72 hr in the presence of phosphonoacetic acid (PAA) and 24 hr in the presence of cycloheximide added at the time of infection. With the use of DNA probes representing about 80% of the MDV genome, an extensive Northern blot analysis of the RNA was carried out. A similar analysis was done with RNA extracted from the MDV-transformed cell line MSB-1. This study revealed 42, 25 and 29 discrete viral RNA transcripts in MDV-Z and MDV-B-infected DEF and in the MSB-1 cell line, respectively, ranging in size from 0.8 to 13 kb. In MDV-Z-infected DEF, there were twelve late RNA species, two early and eight immediate-early viral transcripts. In MDV-B-infected DEF there were eleven late RNA species, two early and seven immediate-early viral transcripts. The RNA species were homologous for all the probes used except the BamHI-G DNA fragment where no RNA transcripts were detected in the MSB-1 cell line. The RNA transcripts were used to produce a preliminary viral RNA map. Comparison of the location and sizes of the viral RNA transcripts in MDV-infected and MDV-transformed cells revealed several differences.

Three mutations in BRCA1 (185delAG, 5382InsC) and BRCA2 (6174delT) predominate among high risk breast ovarian cancer Ashkenazi Jewish families, with few "private" mutations described. Additionally, the spectrum of BRCA1 and BRCA2 germline mutations among high risk Jewish non Ashkenazi and non Jewish Israelis is undetermined. Genotyping by exon-specific sequencing or heteroduplex analysis using enhanced mismatch mutation analysis was applied to 250 high risk, predominantly cancer affected, unrelated Israeli women of Ashkenazi (n = 72), non Ashkenazi (n = 90), Moslem (n = 45), Christian Arabs (n = 21), Druze (n = 17), and non Jewish Caucasians (n = 5). All Jewish women were prescreened and did not harbor any of the predominant BRCA1 or BRCA2 Jewish mutations. Age at diagnosis of breast cancer (median ± SD) (n = 219) was 40.1 ± 11.7, 45.6 ± 10.7, 38.7 ± 9.2, 45.5 ± 11.4 ± and 40.7 ± 8.1 years for Ashkenazi, non Ashkenazi, Moslem, Christian, and Druze participants, respectively. For ovarian cancer (n = 19) the mean ages were 45.75 ± 8.2, 57.9 ± 10.1, 54 ± 8, 70 ± 0, and 72 ± 0 for these origins, respectively. Overall, 22 (8.8%) participants carried 19 clearly pathogenic mutations-10 BRCA1 and 9 BRCA2 (3 novel): 3 in Ashkenazim, 6 in 8 non-Ashkenazim, 6 in 7 Moslems, 2 in Druze, and 2 in non Jewish Caucasians. Only three mutations (c.1991del4, C61G, A1708E) were detected in 2 seemingly unrelated families of Moslem and non- Ashkenazi origins. There were no inactivating mutations among 55 Ashkenazi high risk breast cancer only families. In conclusion, there are no predominant recurring germline mutations in BRCA1 or BRCA2 genes among ethnically diverse Jewish and non Jewish high risk families in Israel.

We determined the sequence of the coding region of segment A, coding for the viral proteins (VPs) VP2, VP4, and VP3, of a very virulent (vv) infectious bursal disease virus (IBDV) isolated in Israel and named IBDVks. We compared the deduced amino acid sequences of the proteins of the new isolate with those of the same proteins from several IBDV isolates, as published in recent years. The amino acid sequences of VP3 and VP4 of the Israeli isolate were 1.9%-2.3% different from the sequences of their counterparts from classical strains. Thus, the stable region of VP2 of IBDVks was very similar (0-0.68% difference) to the same region of VP2 from vv strains from Europe and Japan but distinct from that of proteins from classical strains from Europe, the United States, and Australia (up to 9.42% divergence), showing that IBDVks is more closely related to the vv strains from Europe and Japan. We found that viruses isolated in recent years resemble each other more than isolates from the same areas isolated a few years earlier. Hence, IBDVks can be categorized in one group with vv new isolates from Europe and Japan. This group has been found to be distinct from new isolates in the United States and strains isolated before the IBDV epidemic during the late 1980s.