10 research outputs found
Screening for Medullary Thyroid Cancer in France: A National Effort
Screening for medullary thyroid cancer (MTC) in France is based on a protocol that has been widely distributed nationally. A network of coordinators utilizing a common questionnaire provides for an effective national screening program. Calcitonin stimulation procedures are systematically used for all first-degree relatives of MTC patients. Pathological studies utilize special immunopathologic techniques. Genealogic information is obtained on all index cases, and blood specimens are collected for establishing permanent cell lines. The data collected are used not only to establish the diagnosis of the hereditary or sporadic form of the disease but also to expand the screening as appropriate. This common protocol has benefited patients and their families by improving early detection of cases, increasing the number of families available for follow-up, and improving the prognosis of this cancer. Studies on these families have contributed significantly to the localization of the multiple endocrine neoplasia type 2 gene
JEZIČNA MIKROEVOLUCIJA OTOKA SILBE I OLIBA (analiza bazičnog rječnika)
Istraženi su bazični rječnici selâ Silbe i Oliba. Lingvistička analiza utemeljena na srodnostima pokazuje statistički značajnu razliku između ta dva otoka koji su geografski blizu. Postojeće jezične razlike objašnjavaju se povijesnim seobama stanovništva, različitim ekonomskim orijentacijama i demografskim čimbenicima
Linkage disequilibrium between the four most common cystic fibrosis mutations and microsatellite haplotypes in the Celtic population of Brittany
Microsatellite haplotypes were determined for 117 chromosomes carrying the four most frequent mutations in the cystic fibrosis (CF) gene identified in the Breton population of Celtic origin, as well as for 83 normal chromosomes (noncarriers of a CF mutation). Each of the three non-Delta F508 mutations was associated with a single haplotype: 1078delT with 16-31-13, G551D with 16-7-17, and W846X with 16-32-13. Although these results suggest identity-by-descent for each mutation, recurrent mutations, although unlikely, could not be completely ruled out. The four most frequent haplotypes on normal chromosomes and the three most frequent haplotypes on Delta F508 chromosomes are the same as those found in Ireland, Spain, and Italy. This suggests that some haplotypes, associated or not with the Delta F508 mutation, were present in an ancestral population from which all four populations descended
Familial Deafness, Congenital Heart Defects, and Posterior Embryotoxon Caused by Cysteine Substitution in the First Epidermal-Growth-Factor–Like Domain of Jagged 1
In the present study, we report a kindred with hearing loss, congenital heart defects, and posterior embryotoxon, segregating as autosomal dominant traits. Six of seven available affected patients manifested mild-to-severe combined hearing loss, predominantly affecting middle frequencies. Two patients were diagnosed with vestibular pathology. All patients had congenital heart defects, including tetralogy of Fallot, ventricular septal defect, or isolated peripheral pulmonic stenosis. No individual in this family met diagnostic criteria for any previously described clinical syndrome. A candidate-gene approach was undertaken and culminated in the identification of a novel Jagged 1 (JAG1) missense mutation (C234Y) in the first cysteine of the first epidermal-growth-factor–like repeat domain of the protein. JAG1 is a cell-surface ligand in the Notch signaling pathway. Mutations in JAG1 have been identified in patients with Alagille syndrome. Our findings revealed a unique phenotype with highly penetrant deafness, posterior embryotoxon, and congenital heart defects but with variable expressivity in a large kindred, which demonstrates that mutation in JAG1 can cause hearing loss
Phylogeography of Y-chromosome haplogroup I reveals distinct domains of prehistoric gene flow in Europe
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 ∼9,000 years ago
Disuniting uniformity: A pied cladistic canvas of mtDNA haplogroup H in Eurasia
It has been often stated that the overall pattern of human maternal
lineages in Europe is largely uniform. Yet this uniformity may also
result from an insufficient depth and width of the phylogenetic
analysis, in particular of the predominant western Eurasian haplogroup
(Hg) H that comprises nearly a half of the European mitochondrial DNA
(mtDNA) pool. Making use of the coding sequence information from 267
mtDNA Hg H sequences, we have analyzed 830 mtDNA genomes, from 11
European, Near and Middle Eastern, Central Asian, and Altaian
populations. In addition to the seven previously specified
subhaplogroups, we define fifteen novel subclades of Hg H present in the
extant human populations of western Eurasia. The refinement of the
phylogenetic resolution has allowed us to resolve a large number of
homoplasies in phylogenetic trees of Hg H based on the first
hypervariable segment (HVS-I) of mtDNA. As many as 50 out of 125
polymorphic positions in HVS-I were found to be mutated in more than one
subcluster of Hg H. The phylogeographic analysis revealed that sub-Hgs
H1*, H1b, H1f, H2a, H3, H6a, H6b, and H8 demonstrate distinct
phylogeographic patterns. The monophyletic subhaplogroups of Hg H
provide means for further progress in the understanding of the
(pre)historic movements of women in Eurasia and for the understanding of
the present-day genetic diversity of western Eurasians in general
The western and eastern roots of the Saami - The story of genetic “outliers” told by mitochondrial DNA and Y chromosomes
The Saami are regarded as extreme genetic outliers among European
populations. In this study, a high-resolution phylogenetic analysis of
Saami genetic heritage was undertaken in a comprehensive context,
through use of maternally inherited mitochondrial DNA ( mtDNA) and
paternally inherited Y-chromosomal variation. DNA variants present in
the Saami were compared with those found in Europe and Siberia, through
use of both new and previously published data from 445 Saami and 17,096
western Eurasian and Siberian mtDNA samples, as well as 127 Saami and
2,840 western Eurasian and Siberian Y-chromosome samples. It was shown
that the “Saami motif” variant of mtDNA haplogroup U5b is present in
a large area outside Scandinavia. A detailed phylogeographic analysis of
one of the predominant Saami mtDNA haplogroups, U5b1b, which also
includes the lineages of the “Saami motif,” was undertaken in 31
populations. The results indicate that the origin of U5b1b, as for the
other predominant Saami haplogroup, V, is most likely in western, rather
than eastern, Europe. Furthermore, an additional haplogroup (H1) spread
among the Saami was virtually absent in 781 Samoyed and Ob-Ugric
Siberians but was present in western and central European populations.
The Y-chromosomal variety in the Saami is also consistent with their
European ancestry. It suggests that the large genetic separation of the
Saami from other Europeans is best explained by assuming that the Saami
are descendants of a narrow, distinctive subset of Europeans. In
particular, no evidence of a significant directional gene flow from
extant aboriginal Siberian populations into the haploid gene pools of
the Saami was found