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F Calafell

Publications and source records attributed to F Calafell.

At least 37 records · Page 2Linked to original sources
PubMed2003

Advanced glossary on genetic epidemiology.

This is the last of a series of glossaries on terms used in genetic epidemiology published by the journal. This glossary covers the most advanced genetic terms, most of which are related to new study designs and laboratory techniques. It provides the reader with examples and references of real studies that applied each of the study designs defined in the glossary. This should help the reader grasp the subtleties of each of these strategies and will allow the reader to research the literature according to their interest.

Epidemiology↗
PubMed2002

Haplotype analysis and phylogeny of ornithine transcarbamylase polymorphisms.

Ornithine transcarbamylase (OT2, EC 2.1.3.3) deficiency, the most common inborn error of urea cycle, is caused by a vast number of point mutations, deletions and insertions in the respective gene. Furthermore, 12 single nucleotide polymorphisms (NSPs) have been described in the OTC gene, four of them causing an amino acid change. We have studied the frequency of these markers in two populations: Portuguese and Mozambican. No significant differences were observed between populations, except for Lys --> Arg in codon 46. Allelic associations between polymorphisms were used to define haplotypic patterns. The three common haplotypes (H1, H2 and H3) show a combined frequency of 95% in Portugal and 87% in Mozambique. One haplotype was found only in Portugal and three are only present in Mozambique, resulting in a higher haplotype diversity. The combined information from the SNPs and the DXS1068 (CA)n repeat was used to outline OTC haplotype phylogeny, which, in conjunction with the population data, allowed us to sketch possible evolutionary pathways although some haplotypes could have arisen by either repeated mutation or recombination.

Alleles↗
PubMed2001

Origins and divergence of the Roma (gypsies).

The identification of a growing number of novel Mendelian disorders and private mutations in the Roma (Gypsies) points to their unique genetic heritage. Linguistic evidence suggests that they are of diverse Indian origins. Their social structure within Europe resembles that of the jatis of India, where the endogamous group, often defined by profession, is the primary unit. Genetic studies have reported dramatic differences in the frequencies of mutations and neutral polymorphisms in different Romani populations. However, these studies have not resolved ambiguities regarding the origins and relatedness of Romani populations. In this study, we examine the genetic structure of 14 well-defined Romani populations. Y-chromosome and mtDNA markers of different mutability were analyzed in a total of 275 individuals. Asian Y-chromosome haplogroup VI-68, defined by a mutation at the M82 locus, was present in all 14 populations and accounted for 44.8% of Romani Y chromosomes. Asian mtDNA-haplogroup M was also identified in all Romani populations and accounted for 26.5% of female lineages in the sample. Limited diversity within these two haplogroups, measured by the variation at eight short-tandem-repeat loci for the Y chromosome, and sequencing of the HVS1 for the mtDNA are consistent with a small group of founders splitting from a single ethnic population in the Indian subcontinent. Principal-components analysis and analysis of molecular variance indicate that genetic structure in extant endogamous Romani populations has been shaped by genetic drift and differential admixture and correlates with the migrational history of the Roma in Europe. By contrast, social organization and professional group divisions appear to be the product of a more recent restitution of the caste system of India.

DNA, Mitochondrial↗
PubMed2001

Genetic studies of the Roma (Gypsies): a review.

BACKGROUND: Data provided by the social sciences as well as genetic research suggest that the 8-10 million Roma (Gypsies) who live in Europe today are best described as a conglomerate of genetically isolated founder populations. The relationship between the traditional social structure observed by the Roma, where the Group is the primary unit, and the boundaries, demographic history and biological relatedness of the diverse founder populations appears complex and has not been addressed by population genetic studies. RESULTS: Recent medical genetic research has identified a number of novel, or previously known but rare conditions, caused by private founder mutations. A summary of the findings, provided in this review, should assist diagnosis and counselling in affected families, and promote future collaborative research. The available incomplete epidemiological data suggest a non-random distribution of disease-causing mutations among Romani groups. CONCLUSION: Although far from systematic, the published information indicates that medical genetics has an important role to play in improving the health of this underprivileged and forgotten people of Europe. Reported carrier rates for some Mendelian disorders are in the range of 5-15%, sufficient to justify newborn screening and early treatment, or community-based education and carrier testing programs for disorders where no therapy is currently available. To be most productive, future studies of the epidemiology of single gene disorders should take social organisation and cultural anthropology into consideration, thus allowing the targeting of public health programs and contributing to the understanding of population structure and demographic history of the Roma.

Journal Article↗
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

Profiles of accepted mutation: from neutrality in a pseudogene to disease-causing mutation on its homologous gene.

We have compared the substitution pattern of the glucocerebrosidase gene (GBA) and the glucocerebrosidase pseudogene (psGBA), two highly homologous regions under different selective pressures and within the same genomic background. Mutations in GBA may lead to Gaucher disease, an inborn metabolic disorder. Disease-causing mutations and neutral variation in the gene have been compared to neutral variation in the pseudogene. This comparison offers a unique opportunity to better understand the action of purifying selection, since the differences between mutational patterns can be attributed to different selective pressures. A similar frequency of CpG dinucleotides was observed in GBA and in psGBA, and CpG pairs were mutated with the same high frequency in both regions. However, nucleotides not in CpG pairs were more likely to contribute to disease-causing mutation than to accepted polymorphisms. This pattern, which resulted in a lower transition to transversion ratio in the gene, may be due to CpG avoidance on critical regions within exons.

Base Composition↗
PubMed2001

MtDNA from extinct Tainos and the peopling of the Caribbean.

Tainos and Caribs were the inhabitants of the Caribbean when Columbus reached the Americas; both human groups became extinct soon after contact, decimated by the Spaniards and the diseases they brought. Samples belonging to pre-Columbian Taino Indians from the La Caleta site (Dominican Republic) have been analyzed, in order to ascertain the genetic affinities of these groups in relation to present-day Amerinds, and to reconstruct the genetic and demographic events that took place during the peopling of the Caribbean. Twenty-seven bone samples were extracted and analyzed for mtDNA variation. The four major Amerindian mtDNA lineages were screened through amplification of the specific marker regions and restriction enzymatic digestion, when needed. The HVRI of the control region was amplified with four sets of overlapping primers and sequenced in 19 of the samples. Both restriction enzyme and sequencing results suggest that only two (C and D) of the major mtDNA lineages were present in the sample: 18 individuals (75%) belonged to the C haplogroup, and 6 (25%) to the D haplogroup. Sequences display specific substitutions that are known to correlate with each haplogroup, a fact that helped to reject the possibility of European DNA contamination. A low rate of Taq misincorporations due to template damage was estimated from the cloning and sequencing of different PCR products of one of the samples. High frequencies of C and D haplogroups are more common in South American populations, a fact that points to that sub-continent as the homeland of the Taino ancestors, as previously suggested by linguistic and archaeological evidence. Sequence and haplogroup data show that the Tainos had a substantially reduced mtDNA diversity, which is indicative of an important founder effect during the colonization of the Caribbean Islands, assumed to have been a linear migratory movement from mainland South America following the chain configuration of the Antilles.

Asian People↗
PubMed2001

Patterns of inter- and intra-group genetic diversity in the Vlax Roma as revealed by Y chromosome and mitochondrial DNA lineages.

Previous genetic studies, supported by linguistic and historical data, suggest that the European Roma, comprising a large number of socially divergent endogamous groups, may be a complex conglomerate of founder populations. The boundaries and characteristics of such founder populations and their relationship to the currently existing social stratification of the Roma have not been investigated. This study is an attempt to address the issues of common vs independent origins and the history of population fissioning in three Romani groups that are well defined and strictly endogamous relative to each other. According to linguistic classifications, these groups belong to the Vlax Roma, who account for a large proportion of the European Romani population. The analysis of mtDNA sequence variation has shown that a large proportion of maternal lineages are common to the three groups. The study of a set of Y chromosome markers of different mutability has revealed that over 70% of males belong to a single lineage that appears unique to the Roma and presents with closely related microsatellite haplotypes and MSY1 codes. The study unambiguously points to the common origins of the three Vlax groups and the recent nature of the population fissions, and provides preliminary evidence of limited genetic diversity in this young founder population.

Base Sequence↗
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↗
PubMed2001

Potential transmission of human polyomaviruses through the gastrointestinal tract after exposure to virions or viral DNA.

The mechanism of human-to-human transmission of the polyomaviruses JC virus (JCV) and BK virus (BKV) has not been firmly established with regard to possible human exposure. JCV and BKV have been found in sewage samples from different geographical areas in Europe, Africa, and the United States, with average concentrations of 10(2) to 10(3) JCV particles/ml and 10(1) to 10(2) BKV particles/ml. Selected polyomavirus-positive sewage samples were further characterized. The JCV and BKV present in these samples were identified by sequencing of the intergenic region (the region found between the T antigen and VP coding regions) of JCV and the VP1 region of BKV. The regulatory region of the JCV and BKV strains found in sewage samples presented archetypal or archetype-like genetic structures, as described for urine samples. The stability (the time required for a 90% reduction in the virus concentration) of the viral particles in sewage at 20 degrees C was estimated to be 26.7 days for JCV and 53.6 days for BKV. The presence of JCV in 50% of the shellfish samples analyzed confirmed the stability of these viral particles in the environment. BKV and JCV particles were also found to be stable at pH 5; however, treatment at a pH lower than 3 resulted in the detection of free viral DNA. Since most humans are infected with JCV and BKV, these data indicate that the ingestion of contaminated water or food could represent a possible portal of entrance of these viruses or polyomavirus DNA into the human population.

Animals↗
PubMed2001

Haplotype evolution and linkage disequilibrium: A simulation study.

We simulated the evolution of a three-site haplotype system, two restriction fragment length polymorphisms flanking one short tandem repeat polymorphism, under five different demographic scenarios, three with constant population size and two with population growth. The simulation was designed to observe the effects of population history, recombination fraction, and mutation rate on allele and haplotype frequencies, haplotype diversity, frequency of ancestral alleles, and linkage disequilibrium. The known ancestral haplotypes were often found at low frequencies and even became extinct after 5, 000 generations, especially with small effective population sizes. The original linkage disequilibrium was eroded and even reversed.

Alleles↗
PubMed2000

Worldwide genetic analysis of the CFTR region.

Mutations at the cystic fibrosis transmembrane conductance regulator gene (CFTR) cause cystic fibrosis, the most prevalent severe genetic disorder in individuals of European descent. We have analyzed normal allele and haplotype variation at four short tandem repeat polymorphisms (STRPs) and two single-nucleotide polymorphisms (SNPs) in CFTR in 18 worldwide population samples, comprising a total of 1,944 chromosomes. The rooted phylogeny of the SNP haplotypes was established by typing ape samples. STRP variation within SNP haplotype backgrounds was highest in most ancestral haplotypes-although, when STRP allele sizes were taken into account, differences among haplotypes became smaller. Haplotype background determines STRP diversity to a greater extent than populations do, which indicates that haplotype backgrounds are older than populations. Heterogeneity among STRPs can be understood as the outcome of differences in mutation rate and pattern. STRP sites had higher heterozygosities in Africans, although, when whole haplotypes were considered, no significant differences remained. Linkage disequilibrium (LD) shows a complex pattern not easily related to physical distance. The analysis of the fraction of possible different haplotypes not found may circumvent some of the methodological difficulties of LD measure. LD analysis showed a positive correlation with locus polymorphism, which could partly explain the unusual pattern of similar LD between Africans and non-Africans. The low values found in non-Africans may imply that the size of the modern human population that emerged "Out of Africa" may be larger than what previous LD studies suggested.

Africa↗
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

Y chromosome STR haplotypes in four populations from northwest Africa.

The eight short tandem repeat (STR) polymorphic systems mapping on the male-specific region of the human Y chromosome, DYS19, DYS388, DYS389I, DYS389II, DYS390, DYS391, DYS392 and DYS393, were typed in four populations from northwest (NW) Africa (Moroccan Arabs, southern Moroccan Berbers, Saharawis and Mozabites). Allele frequency distributions showed statistically significant differences for all loci among all the populations except for DYS19. Complete typing was obtained for 185 chromosomes, which showed 74 different haplotypes. The two most frequent haplotypes were found in 16.2% and 15.1% of the individuals, although the latter was almost exclusively found in the Mozabites. Locus and haplotype informativeness were measured by means of the gene diversity (D). The haplotype diversity ranged from 0.856 (Mozabites) to 0.967 (southern Moroccan Berbers). For some loci, allele frequencies in NW Africans were clearly different from those in Europeans. The most common NW African haplotype was found only in one individual out of a total of 494 Europeans typed for the whole STR set. Thus, NW African and European Y chromosomes are clearly differentiated.

Africa, Northern↗
PubMed2000

The probability distribution of the number of loci indicating exclusion in a core set of STR markers.

The distribution of the number of loci out of the 13 in the CODIS STR set that would show an exclusion (i.e., a genotype set incompatible either with the prosecution hypothesis or with Mendelian transmission) was estimated in different scenarios. The knowledge of this distribution would provide a framework against which casework evidence can be compared. I used allele frequencies in Iberian and in Italian populations to generate individual genotypes at random and to test in 1 million simulation replicates, how many of the 13 loci would give an exclusion in an individual identification case, a paternity case, and a double parenthood case. All three scenarios were tested under an expected overall exclusion, both for unrelated individuals and for cases in which the suspect or the alleged father was the brother of the real culprit or real father. Paternity and double parenthood cases were also tested in the true scenario, with exclusionary loci due to mutation. In individual identification cases, the average number of exclusionary loci was 11.95 with a minimum of 7. This STR set also showed sufficient power to resolve identification cases in which the evidence sample came from a suspect's sib. False paternity cases yielded an average of 7.65 exclusionary loci and exclusions with only one (0.0108%) or two (0.14%) exclusionary loci were obtained only rarely. The cases of exclusion with one locus could lead to likelihood ratios in favour of paternity, while both true and false paternity cases with two exclusionary loci would often lead to non-conclusive likelihood ratios. The average number of exclusionary loci in a paternity case where the alleged father was the real father's brother was 3.82, with a significant number of cases where no exclusions were obtained.

Child↗