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D Comas

Publications and source records attributed to D Comas.

At least 19 recordsLinked to original sources
PubMed2006

Extreme population differences across Neuregulin 1 gene, with implications for association studies.

Neuregulin 1 (NRG1) is one of the most exciting candidate genes for schizophrenia in recent years since its first association with the disease in an Icelandic population. Since then, many association studies have analysed allele and haplotype frequencies in distinct populations yielding varying results: some have replicated the association, although with different alleles or haplotypes being associated, whereas others have failed to replicate the association. These contradictory results might be attributed to population differences in allele and haplotype frequencies. In order to approach this issue, we have typed 13 SNPs across this large 1.4 Mb gene, including two of the SNPs originally found associated with schizophrenia in the Icelandic population, the objective being to discover if the underlying cause of the association discrepancies to date may be due to population-specific genetic variation. The analyses have been performed in a total of 1088 individuals from 39 populations, covering most of the genetic diversity in the human species. Most of the SNPs analysed displayed differing frequencies according to geographical region. These allele differences are especially relevant in two SNPs located in a large intron of the gene, as shown by the extreme F(ST) values, which reveal genetic stratification correlated to broad continental areas. This finding may be indicative of the influence of some local selective forces on this gene. Furthermore, haplotype analysis reveals a clear clustering according to geographical areas. In summary, our findings suggest that NRG1 presents extreme population differences in allele and haplotype frequencies. We have given recommendations for taking this into account in future association studies since this diversity could give rise to erroneous results.

Gene Frequency↗
PubMed2006

Paternal and maternal lineages in the Balkans show a homogeneous landscape over linguistic barriers, except for the isolated Aromuns.

The Balkan Peninsula is a complex cultural mosaic comprising populations speaking languages from several branches of the Indo-European family and Altaic, as well as culturally-defined minorities such as the Aromuns who speak a Romance language. The current cultural and linguistic landscape is a palimpsest in which different peoples have contributed their cultures in a historical succession. We have sought to find any evidence of genetic stratification related to those cultural layers by typing both mtDNA and Y chromosomes, in Albanians, Romanians, Macedonians, Greeks, and five Aromun populations. We have paid special attention to the Aromuns, and sought to test genetically various hypotheses on their origins. MtDNA and Y-chromosome haplogroup frequencies in the Balkans were found to be similar to those elsewhere in Europe. MtDNA sequences and Y-chromosome STR haplotypes revealed decreased variation in some Aromun populations. Variation within Aromun populations was the primary source of genetic differentiation. Y-chromosome haplotypes tended to be shared across Aromuns, but not across non-Aromun populations. These results point to a possible common origin of the Aromuns, with drift acting to differentiate the separate Aromun communities. The homogeneity of Balkan populations prevented testing for the origin of the Aromuns, although a significant Roman contribution can be ruled out.

Chromosomes, Human, Y↗
PubMed2005

Haplotype tagging efficiency in worldwide populations in CTLA4 gene.

The cytotoxic T lymphocyte antigen 4 (CTLA4) acts as a potent negative regulator of T-cell response, and has been suggested as a pivotal candidate gene for autoimmune disorders such as Graves' disease, type 1 diabetes and autoimmune hypothyroidism, among others. Several single-nucleotide polymorphisms (SNPs) have been proposed as the susceptibility variants, or to be in strong linkage disequilibrium (LD) with the variant. Nevertheless, contradictory results have been found, which may be due to lack of knowledge of the genetic structure of CTLA4 and its geographic variation. We have typed 17 SNPs throughout the CTLA4 gene region in order to analyze the haplotype diversity and LD structure in a worldwide population set (1262 individuals from 44 populations) to understand the variation pattern of the region. Allele and haplotype frequency differentiation between populations is consistent with genomewide averages and points to a lack of strong population-specific selection pressures. LD is high and its pattern is not significantly different within or between continents. However, haplotype composition is significantly different between geographical groups. A continent-specific set of haplotype tagging SNPs has been designed to be used for future association studies. These are portable among populations, although their efficiency might vary depending on the population haplotype spectrum.

Alleles↗
PubMed2005

The genetics of the pre-Roman Iberian Peninsula: a mtDNA study of ancient Iberians.

The Iberians developed a surprisingly sophisticated culture in the Mediterranean coast of the Iberian Peninsula from the 6th century BC until their conquest by the Romans in the 2nd century BC. They spoke and wrote a non-Indo-European language that still cannot be understood; their origins and relationships with other non-Indo-European peoples, like the Etruscans, are unclear, since their funerary practices were based on the cremation of bodies, and therefore anthropology has been unable to approach the study of this people. We have retrieved mitochondrial DNA (mtDNA) from a few of the scarce skeletal remains that have been preserved, some of them belonging to ritualistically executed individuals. The most stringent authentication criteria proposed for ancient DNA, such as independent replication, amino-acid analysis, quantitation of template molecules, multiple extractions and cloning of PCR products, have been followed to obtain reliable sequences from the mtDNA hypervariable region 1 (HVR1), as well as some haplogroup diagnostic SNPs. Phylogeographic analyses show that the haplogroup composition of the ancient Iberians was very similar to that found in modern Iberian Peninsula populations, suggesting a long-term genetic continuity since pre-Roman times. Nonetheless, there is less genetic diversity in the ancient Iberians than is found among modern populations, a fact that could reflect the small population size at the origin of the population sampled, and the heterogenic tribal structure of the Iberian society. Moreover, the Iberians were not especially closely related to the Etruscans, which points to considerable genetic heterogeneity in Pre-Roman Western Europe.

Adult↗
PubMed2004

Alu insertion polymorphisms in the Balkans and the origins of the Aromuns.

We have analysed 11 human-specific Alu insertion polymorphisms in the Balkans to elucidate the origins of the Aromuns, a linguistic isolate inhabiting scattered areas in the Balkan Peninsula. Four Aromun samples (two from the Republic of Macedonia, one from Albania, and one from Romania) and five neighbouring populations (Macedonians, Albanians, Romanians, Greeks, and Turks) were analysed by means of genetic distances, principal components and analyses of the molecular variance (AMOVA). Three hypotheses were tested: Aromuns are Romanophonic Greeks; the result of a Romanian southward migration; or local descendants of the Thracians. The analyses show that the Aromuns do not constitute a homogeneous group separated from the rest of the Balkan populations. Grouping by language or geography does not explain the genetic differences observed in the region, suggesting a lack of genetic structure in the area. Aromuns do not seem to be particularly related to Greeks, Romanians, or to other Romance speakers. The Aromuns might have their origin to the south of the Danube river, with extensive gene flow with the neighbouring populations. The present results suggest a common ancestry of all Balkan populations, including Aromuns, with a lack of correlation between genetic differentiation and language or ethnicity, stressing that no major migration barriers have existed in the making of the complex Balkan human puzzle.

Alu Elements↗
PubMed2004

Mitochondrial DNA heterogeneity in Tunisian Berbers.

Berbers live in groups scattered across North Africa whose origins and genetic relationships with their neighbours are not well established. The first hypervariable segment of the mitochondrial DNA (mtDNA) control region was sequenced in a total of 155 individuals from three Tunisian Berber groups and compared to other North Africans. The mtDNA lineages found belong to a common set of mtDNA haplogroups already described in North Africa. Besides the autochthonous North African U6 haplogroup, a group of L3 lineages characterized by the transition at position 16041 seems to be restricted to North Africans, suggesting that an expansion of this group of lineages took place around 10500 years ago in North Africa, and spread to neighbouring populations. Principal components and the coordinate analyses show that some Berber groups (the Tuareg, the Mozabite, and the Chenini-Douiret) are outliers within the North African genetic landscape. This outlier position is consistent with an isolation process followed by genetic drift in haplotype frequencies, and with the high heterogeneity displayed by Berbers compared to Arab samples as shown in the AMOVA. Despite this Berber heterogeneity, no significant differences were found between Berber and Arab samples, suggesting that the Arabization was mainly a cultural process rather than a demographic replacement.

DNA, Mitochondrial↗
PubMed2003

Possible increased risk for Alzheimer's disease associated with neprilysin gene.

Neprilysin has recently been reported to be the major physiological Abeta-degradating enzyme. In this study we describe a new biallelic polymorphism in the 3'UTR of the neprilysin gene in a representative population sample. The (*)159C/C genotype was found to be associated with an increased risk for Alzheimer's disease in an age-dependent manner. Adjusting for sex and APOE status, an odds ratio of 2.74 (p < 0.05) was observed among patients under 75 years old.

3' Untranslated Regions↗
PubMed2003

Association of the CTLA4 promoter region (-1661G allele) with type 1 diabetes in the South Moroccan population.

The contribution of the candidate gene CTLA4 to type 1 diabetes is not well established. Although several polymorphisms have been repeatedly associated to the disease, several studies have not confirmed the association. The joint analysis of three SNPs in the CTLA4 promoter region (-1722, -1661, and -319), one SNP in the first exon (+49), and one dinucleotide repeat in the 3' untranslated region, in a case-control study in a North African population, shows a strong association of the CTLA4 region with the disease. The -1661G allele showed a significant association with an odds ratio of 2.13. Moreover, the internal structure of the dinucleotide repeat has been deeply analyzed. The present results reveal the importance of polymorphisms in the CTLA4 promoter region, their probable role in gene expression and, ultimately, their relation to the etiology of type 1 diabetes. Previous contradictory association studies might be due to the effect of linkage disequilibrium between the polymorphism analyzed and the alteration within the CTLA4 region. This alteration may be different depending on the genetic background of the population. The present work stresses the need to perform exhaustive analysis of the promoter region polymorphisms in order to detect association with the disease.

Alleles↗
PubMed2003

Joining the pillars of Hercules: mtDNA sequences show multidirectional gene flow in the western Mediterranean.

Phylogenetic analysis of mitochondrial DNA (mtDNA) performed in Western Mediterranean populations has shown that both shores share a common set of mtDNA haplogroups already found in Europe and the Middle East. Principal co-ordinates of genetic distances and principal components analyses based on the haplotype frequencies show that the main genetic difference is attributed to the higher frequency of sub-Saharan L haplogroups in NW Africa, showing some gene flow across the Sahara desert, with a major impact in the southern populations of NW Africa. The AMOVA demonstrates that SW European populations are highly homogeneous whereas NW African populations display a more heterogeneous genetic pattern, due to an east-west differentiation as a result of gene flow coming from the East. Despite the shared haplogroups found in both areas, the European V and the NW African U6 haplogroups reveal the traces of the Mediterranean Sea permeability to female migrations, and allowed for determination and quantification of the genetic contribution of both shores to the genetic landscape of the geographic area. Comparison of mtDNA data with autosomal markers and Y-chromosome lineages, analysed in the same populations, shows a congruent pattern, although female-mediated gene flow seems to have been more intense than male-mediated gene flow.

Analysis of Variance↗
PubMed2001

Induction of vitellogenin gene transcription in vitro by juvenile hormone in Blattella germanica.

In the cockroach Blattella germanica, the synthesis of vitellogenin is juvenile hormone III (JH III)-dependent. We have studied the effect of JH III upon vitellogenin gene expression in periovaric fat bodies incubated in vitro. Periovaric fat bodies were obtained from cardioallatectomized females. The response to JH III was measured in terms of vitellogenin and vitellogenin mRNA after 7 h of incubation. A hormonal concentration as low as 1 nM was enough to induce vitellogenin production and its release to the medium, whereas the concentration of 10 nM produced the maximal effects. Although the response of the vitellogenin gene to JH III is fast and efficient, it seems that the action is mediated by protein factors, given that cycloheximide treatment impairs the hormonal effect. The presence in the medium of brain extract (0.5 equivalents), corpora cardiaca (one pair) or hypertrehalosemic hormone (10(-7) or 10(-8) M), partially inhibited the response to JH III.

Animals↗
PubMed2001

High-resolution analysis of human Y-chromosome variation shows a sharp discontinuity and limited gene flow between northwestern Africa and the Iberian Peninsula.

In the present study we have analyzed 44 Y-chromosome biallelic polymorphisms in population samples from northwestern (NW) Africa and the Iberian Peninsula, which allowed us to place each chromosome unequivocally in a phylogenetic tree based on >150 polymorphisms. The most striking results are that contemporary NW African and Iberian populations were found to have originated from distinctly different patrilineages and that the Strait of Gibraltar seems to have acted as a strong (although not complete) barrier to gene flow. In NW African populations, an Upper Paleolithic colonization that probably had its origin in eastern Africa contributed 75% of the current gene pool. In comparison, approximately 78% of contemporary Iberian Y chromosomes originated in an Upper Paleolithic expansion from western Asia, along the northern rim of the Mediterranean basin. Smaller contributions to these gene pools (constituting 13% of Y chromosomes in NW Africa and 10% of Y chromosomes in Iberia) came from the Middle East during the Neolithic and, during subsequent gene flow, from Sub-Saharan to NW Africa. Finally, bidirectional gene flow across the Strait of Gibraltar has been detected: the genetic contribution of European Y chromosomes to the NW African gene pool is estimated at 4%, and NW African populations may have contributed 7% of Iberian Y chromosomes. The Islamic rule of Spain, which began in a.d. 711 and lasted almost 8 centuries, left only a minor contribution to the current Iberian Y-chromosome pool. The high-resolution analysis of the Y chromosome allows us to separate successive migratory components and to precisely quantify each historical layer.

Africa South of the Sahara↗
PubMed2001

Glucocerebrosidase pseudogene variation and Gaucher disease: Recognizing pseudogene tracts in GBA alleles.

We surveyed the genetic variability of the glucocerebrosidase pseudogene (psGBA) in a worldwide sample of 100 human chromosomes. psGBA is the non-functional duplicate of the gene responsible for Gaucher disease (GBA), the most common lipid storage disorder. The existence of only one psGBA allele described until now, together with the high homology between GBA and psGBA, often prevented recognition of the complex alleles formed by the combination of GBA and psGBA, because psGBA variants could be confused with GBA mutations. In order to determine the variability existent in psGBA, the whole psGBA DNA segment was PCR-amplified and sequenced, and the genotype for all samples was obtained. The ascertainment of the phase among the heterozygous sites was possible through cloning and sequencing a single allele. Eighteen variable sites were detected along psGBA. Two of the variants already have been reported as Gaucher-causing mutations when present in GBA alleles. The other variants were unknown. The knowledge of the psGBA variants described in this report will allow identification of psGBA-GBA complex alleles that may aid in understanding the intricate phenotype-genotype relationship in Gaucher disease.

Alleles↗
PubMed2001

Colonization and bacteremia risk factors in parenteral nutrition catheterization.

AIMS: 1) To establish the relationship between the kind of microorganism that colonizes parenteral nutrition catheters and several risk factors related to catheterization and patient characteristics. 2) To investigate the risk factors associated to bacteremia episodes originated in these colonized catheters. METHOD: An observational, non-controlled, retrospective and cohorts study of the parenteral nutrition catheters implanted between 1988 and 1994 in our hospital. Risk factors were studied in 6 multiple-logistic regression models. RESULTS: 3632 catheters were studied. Incidences of colonization and bacteremia per 1000 days of catheterization were 17.56 and 3.93, respectively. Coagulase-negative staphyloccoci (CNS) were the most frequently isolated microorganisms. The colonization risk factors were: insertion site for all the microorganisms except fungi, catheterization time for CNS and fungi, hospitalization area, sex and age for CNS model, the existence of other infectious foci for Gram negative bacilli (GNB), S. aureus and other microorganisms, hypoalbuminemia for GNB model, and neoplasm for other microorganisms. The bacteremia risk factors were jugular insertion site, catheterization time greater than 10 days, catheter's hub colonization, and catheter colonization by gram-negative bacilli, fungi and S. aureus. CONCLUSION: Risk factors for catheter colonization vary depending on the microorganism which colonizes the catheter.

Adult↗
PubMed2001

Sequence variability of a human pseudogene.

We have obtained haplotypes from the autosomal glucocerebrosidase pseudogene (psGBA) for 100 human chromosomes from worldwide populations, as well as for four chimpanzee and four gorilla chromosomes. In humans, in a 5420-nucleotide stretch analyzed, variation comprises 17 substitutions, a 3-bp deletion, and a length polymorphism at a polyadenine tract. The substitution rate on the pseudogene (1.23 +/- 0.22 x 10(-9) per nucleotide and year) is within the range of previous estimates considering phylogenetic estimations. Recombination within the pseudogene was recognized, although the low variability of this locus prevented an accurate measure of recombination rates. At least 13% of the psGBA sequence could be attributed to gene conversion from the contiguous GBA gene, whereas the reciprocal event has been shown to lead to Gaucher disease. Human psGBA sequences showed a recent coalescence time (approximately 200,000 yr ago), and the most ancestral haplotype was found only in Africans; both observations are compatible with the replacement hypothesis of human origins. In a deeper timeframe, phylogenetic analysis showed that the duplication event that created psGBA could be dated at approximately 27 million years ago, in agreement with previous estimates.

Animals↗
PubMed2000

Georgian and kurd mtDNA sequence analysis shows a lack of correlation between languages and female genetic lineages.

Mitochondrial DNA sequences from Georgians and Kurds were analyzed in order to test the possible correlation between female lineages and languages in these two neighboring West Eurasian groups. Mitochondrial sequence pools in both populations are very similar despite their different linguistic and prehistoric backgrounds. Both populations present mtDNA lineages that clearly belong to the European gene pool, as shown by 1) similar nucleotide and sequence diversities; 2) a large number of sequences shared with the rest of European samples; 3) nonsignificant genetic distances; and 4) classification of the present lineages into the major European mtDNA haplogroups already described. The outlier position of the populations from the Caucasus according to classical genetic markers is not recognized in the present Georgian mtDNA sequence pool. This result suggests that the differentiation of mtDNA sequences in West Eurasia and the outlier features of Caucasian populations should be attributed to different processes. Moreover, the putative linguistic relationship between Caucasian groups and the Basques, another outlier population within Europe for classical genetic markers, is not detected by the analysis of mtDNA sequences.

Adult↗
PubMed2000

Vitellogenin of Blattella germanica (L.) (Dictyoptera, blattellidae): nucleotide sequence of the cDNA and analysis of the protein primary structure.

The cloning and sequencing of a cDNA of the vitellogenin gene from the cockroach Blattella germanica is reported. It is 5,749 nucleotides long and encodes an amino acid sequence of 1,862 residues (including a putative signal peptide of 17 residues). The vitellogenin sequence includes a long serine-rich stretch between amino acids 322 and 349, and two other stretches between amino acids 1691 and 1740. The vitellogenin of B. germanica shows a notable similarity (between 32 and 42%) to those described in other insects, and its alignment shows a high number of motifs conserved in all species, especially in the subdomains I-V. Non-parsimony methods (Neighbor Joining) of phylogenetic analysis of the insect vitellogenin sequences gave a tree showing a topology that is, in general, congruent with the currently accepted insect phylogenetic schemes. Arch.

Amino Acid Sequence↗