To investigate which aspects of contemporary human Y-chromosome variation in Europe are characteristic of primary colonization, late-glacial expansions from refuge areas, Neolithic dispersals, or more recent events of gene flow, we have analyzed, in detail, haplogroup I (Hg I), the only major clade of the Y phylogeny that is widespread over Europe but virtually absent elsewhere. The analysis of 1,104 Hg I Y chromosomes, which were identified in the survey of 7,574 males from 60 population samples, revealed several subclades with distinct geographic distributions. Subclade I1a accounts for most of Hg I in Scandinavia, with a rapidly decreasing frequency toward both the East European Plain and the Atlantic fringe, but microsatellite diversity reveals that France could be the source region of the early spread of both I1a and the less common I1c. Also, I1b*, which extends from the eastern Adriatic to eastern Europe and declines noticeably toward the southern Balkans and abruptly toward the periphery of northern Italy, probably diffused after the Last Glacial Maximum from a homeland in eastern Europe or the Balkans. In contrast, I1b2 most likely arose in southern France/Iberia. Similarly to the other subclades, it underwent a postglacial expansion and marked the human colonization of Sardinia approximately 9,000 years ago.

The extent and nature of southeastern Europe (SEE) paternal genetic contribution to the European genetic landscape were explored based on a high-resolution Y chromosome analysis involving 681 males from seven populations in the region. Paternal lineages present in SEE were compared with previously published data from 81 western Eurasian populations and 5,017 Y chromosome samples. The finding that five major haplogroups (E3b1, I1b* (xM26), J2, R1a, and R1b) comprise more than 70% of SEE total genetic variation is consistent with the typical European Y chromosome gene pool. However, distribution of major Y chromosomal lineages and estimated expansion signals clarify the specific role of this region in structuring of European, and particularly Slavic, paternal genetic heritage. Contemporary Slavic paternal gene pool, mostly characterized by the predominance of R1a and I1b* (xM26) and scarcity of E3b1 lineages, is a result of two major prehistoric gene flows with opposite directions: the post-Last Glacial Maximum R1a expansion from east to west, the Younger Dryas-Holocene I1b* (xM26) diffusion out of SEE in addition to subsequent R1a and I1b* (xM26) putative gene flows between eastern Europe and SEE, and a rather weak extent of E3b1 diffusion toward regions nowadays occupied by Slavic-speaking populations.

In this association study the authors compared the insertion/deletion (I/D) angiotensin-I converting enzyme (ACE) gene polymorphism in females and males with premature myocardial infarction (MI). I/D ACE gene polymorphism was tested in 738 subjects: 302 patients with MI (151 men and 151 women) and 436 healthy subjects (207 men and 229 women). In women the ACE-DD genotype was not associated with MI (OR 1.1, 95% CI 0.6-2.1, p=0.6), whereas the ACE-DD genotype conferred a 2-fold independent risk for MI in men (95% CI=1.2-3.4; p=0.013) after adjustment for cardiovascular risk factors. The authors found evidence for the sex difference in the effect of the ACE-DD genotype on MI risk. The ACE-DD genotype conferred a 2-fold independent risk for premature MI in males.

The 1691 (G>A) factor V Leiden (FVL) and 20210 (G>A) prothrombin (PT) mutations are the two most common genetic risk factors in venous thromboembolism. The 677 (C>T) methylene tetrahydrofolate reductase (MTHFR) mutation is the most frequently mentioned as an independent genetic risk factor for venous thromboembolism. As there are limited published data on the prevalence of the 1691, 20210 and 677 mutations in our population, the aim of this study was to determine the frequencies and association of these deep vein thrombosis mutations in the Bosnian population.This study included 111 thromboembolic patients and 207 healthy subjects with absence of known risk factors for venous thromboembolism. Genotyping of the 1691, 20210 and 677 mutations was done by polymerase chain reaction (PCR), followed by restriction digestion with MnlI, HindIII and HinfI enzymes.Out of the 111 patients, 18.0% were heterozygous and 2.70% were homozygous for the 1691 mutation. Among 207 healthy controls, 3.86%, were heterozygous for the 1691 mutation. This study confirmed the association of the 1691 mutation with deep vein thrombosis in the Bosnian population odds ratio (OR) [95% confidence interval (CI)] = 6.0 (2.62-14.14); p = 0.0001). The 20210 mutation was detected in 2.70% of patients and it was totally absent in the control group. Allele and genotype frequency of 677 did not differ significantly between the cases and controls (χ2 = 1.03; p = 0.309).

In tro duc tion: The re ce nt stu dies of Par kin son's di sea se (PD) in di ca te that ge ne ti cs and en vi ron men tal fac to rs may play an im por ta nt ro le in developi ng of PD. Nowa days, the ce ll dea th and ce ll ad he sion are pat ho genetic mec ha nis ms whi ch cou ld be re la ted wi th PD. On the ba sis of re la tionship of tho se mec ha nis ms wi th PD, the aim of this stu dy was to iden ti fy new can di da te genes for PD by in teg ra tion of re sul ts of tran scrip to mi cs studies and re sul ts ob tai ned by Bio me di cal Dis co ve ry Sup po rt System (BITOLA). Ma te ria ls and met ho ds: For the de tec tion of fun ctio nal re la tion ship be tween po ten tial can di da te ge ne and pat ho ge ne tic mec ha nis ms as so cia ted wi th PD, we de sig ned stra te gy of in teg ra tion of re sul ts of tran scrip to mi cs stu dies wi th dis co ve ry ap proa ch in bib liog rap hic da ta ba ses and BITOLA. Da ta of chro mo so me lo ca tion, tis sue-spe ci fi c expres sion, fun ction of po ten tial can di da te ge nes and their as so cia tion with ge ne ti cs di sor de rs we re ob tai ned from Med li ne, Lo cus Li nk, Ge ne Car ds and OMIM. Re sul ts: In teg ra tion and com pa ri son of re sul ts ob tai ned usi ng the BITOLA system and ana lysis of tran scrip to mi cs stu dies iden ti fi ed six ge nes (MAPT, UC HL1, NSF, CDC42, PAR K2 and GFPT1) that oc cur si mul ta neous ly in bo th group of re sul ts. The fun ction of ge nes NSF, CDC42 and GFPT1 in the pat ho gene sis of PD has not been stu died yet. Con clu sio ns: Accor di ng to our re su lt that afo re men tio ned ge nes ap pea red in bo th grou ps of re sults and par tial ly mat ch the cri te ria set for the selec tion of can di da te ge nes and their po ten tial ro le in the de ve lop me nt of PD, they shou ld be tes ted by met ho ds spe ci fi cal ly in ten ded for tho se three ge nes. Key wor ds: Par kin son's disea se; can di da te ge nes; Bio me di cal Dis co ve ry Sup po rt System (BITOLA) Original article In tro duc tionPar kin son's di sea se (PD) is etio lo gi cal ly, ge ne ti cal ly and pat ho lo gi cal ly com plex and he te ro ge neous di sea se (1). It is es ti ma ted that mo st ca ses of PD (>95%) are spo ra dic and ha ve la te age on set, yet sma ll but growi ng sub set of in di vi dua ls has a single ge ne de fe ct as the cau se of the di sea se (2,3). In the la st group, at lea st ten lo ci as so cia ted wi th PD ha ve been iden ti fied so far: PAR K1, PAR K2, PAR K3, PAR K4, PAR K5, PAR K6, PAR K7, PAR K8, PAR K9 and GBA (4).Ge no me-wi de stu dy of mul tip lex PD fa mi ly off ered evi den ce about con nec tion of tho se lo ci whi ch are on the diff e re nt chro mo so mes (5-7). Ge ne ti cally de fi ned fa mi lial for ms of PD off er in sig hts in to mo le cu lar sig na li ng pat hways that mo du la te protein deg ra da tion and mi toc hon drial ho meos ta sis sus tai ni ng the se lec ti ve neu ro de ge ne ra ti ve pro cess in typi cal Par kin so ni sm (8). Ge ne tic he te ro ge neity of mo no ge nic fo rm of PD poin ts to...