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Biomedical subjects

A Amorim

Publications and source records attributed to A Amorim.

At least 19 recordsLinked to original sources
PubMed2007

Dissecting the genetic history of São Tomé e Príncipe: a new window from Y-chromosome biallelic markers.

Twenty biallelic Y chromosome markers were analyzed in Angolares, Forros and Tongas, three population groups from the African archipelago of São Tomé e Príncipe. While most male lineages belonged to sub-Saharan haplogroups, the component of European origin added up 23.9% in the archipelago. This contrasts with the reported absence of European mtDNA lineages, and the combined findings testify to a strong sex-biased admixture process during the long-lasting colonial period in São Tomé e Príncipe. Furthermore, the male mediated European component was clearly found to be out of proportion to the small demographic impact of the Portuguese on the islands, reflecting high variance in the reproductive success of the individuals that contributed to its peopling. The male portion of European ancestry was 33.3% in Forros, 27.3% in Tongas and approximately two-fold less, 14.5%, in Angolares. The Angolares also showed the lowest haplogroup diversity and the most reduced number of different haplogroups. The current results reinforce our previous evidence pointing to remarkable restrictions in gene flow between Angolares and other São Tomean inhabitants, in agreement with their considerable isolation and confinement to the south-eastern tip of São Tomé until recently.

Africa↗
PubMed2006

Congenital disorder of glycosylation type Ia: searching for the origin of common mutations in PMM2.

Congenital Disorders of Glycosylation (CDG) are a group of recessive genetic disorders characterized by hypoglycosylation of glycoproteins. CDG-Ia, the most common type, is caused by mutations in the PMM2 gene, coding for a phosphomannomutase (PMM2; EC 5.4.2.8). The mutational spectrum of PMM2 comprises more than 80 different mutations but one of them, R141H, is particularly interesting due to its high frequency among CDG-Ia patients worldwide. In contrast, other mutations are ethnically or geographically restricted, such as D65Y which is only found in patients of Iberian ancestry. In the present study a population genetic approach was used in an attempt to clarify the origins of two important disease causing mutations: R141H and D65Y. Based on SNP and STR genotypic analysis, we ascertained an association between the R141H substitution and a particular haplotype, suggesting a common origin for all the mutated chromosomes. Similar results were found for D65Y, although the associated haplotype was different from that of R141H, suggesting independent origins for these two mutations. Our results enable us to infer an Iberian origin for the D65Y mutation.

Carbohydrate Metabolism, Inborn Errors↗
PubMed2006

Mutational spectrum and linkage disequilibrium patterns at the ornithine transcarbamylase gene (OTC).

Ornithine transcarbamylase (OTC; EC 2.1.3.3) is a hepatic enzyme involved in ammonia elimination via the urea cycle. Since the sequence of the OTC gene was reported many types of mutations continue to be found in OTC deficiency patients, continuing to increase the already wide mutational spectrum known for this gene. In this study we present the clinical, biochemical and molecular features of thirteen late-onset OTC deficiency patients. Mutations were identified in all these patients, among which six were novel point substitutions (L59R, A137P, L148S, Y176L, L186P, and K210N) and one was a 2-bp deletion at exon 4 (341-342delAA). In addition, a de novo genomic deletion of maternal origin encompassing exons 1 to 5 was also identified by the analysis of LD patterns using intragenic polymorphic markers. This work exemplifies the potential value of population genetic studies for the detection of large deletions.

Exons↗
PubMed2005

Population data on 15 autosomal STRs in a sample from East Timor.

Allele frequencies for the fifteen STRs included in the AmpF/STR Identifiler (CSF1PO, D2S1338, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D19S433, D21S11, FGA, TH01, TPO and VWA) were estimated from a sample of 186 unrelated individuals from East Timor. No deviations from Hardy-Weinberg equilibrium were observed (only after applying the Bonferroni correction in the cases of D2S1338, TPO and D5S818). Genetic parameters of forensic interest were calculated and comparison with geographically nearby populations was performed.

DNA Fingerprinting↗
PubMed2005

A case of double alleles at three Y-STR loci: forensic implications.

In a genetic study of unrelated donors from Bahia (Brazil), one sample contained a 16 Y-STR haplotype with double peaks at three loci: DYS389 II, DYS437 and DYS439. The son of the subject had the same haplotype as found in the father. This profile was compared with a similar case found in a paternity case investigation in Madrid (Spain) and a match was found for the full 16 Y-STR haplotype. Because these three loci are located within the AZFa segment, these results are in accordance with duplication of the AZFa region that includes also other Y-STRs currently used in forensic investigation, for example DYS389I and DYS438. This case attracts our attention in the forensic interpretation of Y-haplotype profiles, because multiple alleles at various loci do not indicate forcibly that the sample under analysis is a mixture.

Brazil↗
PubMed2005

Data for 15 autosomal STR markers (Powerplex 16 System) from two Tunisian populations: Kesra (Berber) and Zriba (Arab).

Allele frequencies, together with some parameters of forensic interest, for 15 STRs included in the Powerplex 16 System (CSF1PO, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, FGA, Penta D, Penta E, TH01, TPO and VWA) were estimated from two samples of unrelated individuals from Tunisia, of different ethnicity: Kesra (Berber) and Zriba (Arab). No deviations from Hardy-Weinberg equilibrium were observed after Bonferroni's correction for the number of loci analysed. Comparative analyses between our population data and other North African databases showed that significant differences were concentrated on loci with lowest values of diversity (mainly CSF1PO and D13S317), irrespective of ethnicity and geographic location.

DNA Fingerprinting↗
PubMed2005

Mutation rates at Y chromosome specific microsatellites.

A collaborative work was carried out by the Spanish and Portuguese ISFG Working Group (GEP-ISFG) to estimate Y-STR mutation rates. Seventeen Y chromosome STR loci (DYS19, DYS385, DYS389I and II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS460, DYS461, DYS635 [GATA C4], GATA H4, and GATA A10) were analyzed in a sample of 3,026 father/son pairs. Among 27,029 allele transfers, 54 mutations were observed, with an overall mutation rate across the 17 loci of 1.998 x 10(-3) (95% CI, 1.501 x 10(-3) to 2.606 x 10(-3)). With just one exception, all of the mutations were single-step, and they were observed only once per gametogenesis. Repeat gains were more frequent than losses, longer alleles were found to be more mutable, and the mutation rate seemed to increase with the father's age. Hum Mutat 26(6), 520-528, 2005. (c) 2005 Wiley-Liss, Inc.

Age Factors↗
PubMed2005

Novel L2HGDH mutations in 21 patients with L-2-hydroxyglutaric aciduria of Portuguese origin.

We studied 21 patients, from 18 families, with L-2-hydroxyglutaric aciduria (L-2-HGA), a rare neurometabolic disorder with a homogeneous presentation: progressive neurodegeneration with extrapyramidal and cerebellar signs, seizures, and subcortical leukoencephalopathy. Increased levels of L-2-hydroxyglutaric acid in body fluids proved the diagnosis of L-2-HGA in all 21 patients. We analyzed the L-2-HGA gene (L2HGDH), recently found to be mutated in consanguineous families with L-2-HGA, and identified seven novel mutations in 15 families. Three mutations appeared to be particularly prevalent in this Portuguese panel: a frameshift mutation (c.529delC) was detected in 12 out of 30 mutant alleles (40%), a nonsense mutation (c.208C>T; p.Arg70X) in 7/30 alleles (23%), and a missense mutation (c.293A>G; p.His98Arg) in four out of 30 mutant alleles (13%), suggesting that common origin may exist. Furthermore, two novel missense (c.169G>A; p.Gly57Arg, c.1301A>C; p.His434Pro) and two splice error (c.257-2A>G, c.907-2A>G) mutations were found. All the mutations presumably lead to loss-of-function with no relationship between clinical signs, progression of the disease, levels of L-2-HGA and site of the mutation. In the three remaining families, no pathogenic mutations in the L-2-HGA were found, which suggests either alterations in regulatory regions of the gene or of its intervening sequences, compound heterozygosity for large genomic deletion and, or further genetic heterogeneity.

Adolescent↗
PubMed2005

mtDNA single macrodeletions associated with myopathies: absence of haplogroup-related increased risk.

As for any non-recombining genome, any mutation at mtDNA, if not recurrent, appears on a particular haplotype background, allowing its detection by haplogroup association studies. It has been shown that the propensity for occurrence of single macrodeletions at a level beyond the pathological threshold is associated with super-haplogroup U/K. However, in this report, we present evidence for the absence of preferential haplogroup backgrounds for single macrodeletions. We have analysed how haplogroup diagnostic polymorphisms could disrupt direct repeats usually flanking the deleted segment, and we have concluded that for the Common Deletion, no such polymorphisms are observed in humans, but they do occur in other primates. Furthermore, we also report five new single macrodeletions.

Adolescent↗
PubMed2005

The mtDNA catalogue of all Portuguese autochthonous goat (Capra hircus) breeds: high diversity of female lineages at the western fringe of European distribution.

Goat is believed to be the first true livestock domesticated and, apart from its historical importance, keeps playing an essential economic role in very diverse human societies. We have analysed the female gene pool of all Portuguese autochthonous breeds (Bravia, Serrana, Charnequeira, Serpentina and Algarvia) through the mtDNA HVI sequencing of 288 unrelated animals sampled throughout the country. All breeds proved to be extremely diverse (average haplotype diversity of 0.977), in contrast with the Portuguese peripheral geographic situation in the distribution range of the species. Moreover, observed genetic distances between breeds do not correlate with microgeography inside Portugal. These observations are consistent with recurrent refreshment of the breeding stock through the introduction of exotic animals. Fitting the new data into the still loosely defined female genetic pool landscape of goats, all Portuguese animals, one sample excepted (belonging to Bravia), are classified into haplogroup A and haplotype sharing is geographically very sparse, including a Far East match. Our results confirm that goats stand out among most of domesticates as exceptionally diverse and showing an unparalleled degree of mobility of animals (at least females) used for reproductive purposes.

Analysis of Variance↗
PubMed2005

Mitochondrial DNA haplotyping revealed the presence of mixed up benign and neoplastic tissue sections from two individuals on the same prostatic biopsy slide.

DNA typing was requested to investigate a presumptive cancer diagnosis error by confirming whether benign and cancerous prostatic tissue in the same presurgical haematoxylin and eosin stained slide belonged to the same person. After independent histological re-examination of the slide by a pathologist, manual slide dissection was used to guarantee independent and high recovery DNA isolation from each tissue section, avoiding carryover and background contamination. Nuclear DNA quantification performed by real time polymerase chain reaction (PCR) revealed the absence of human DNA for short tandem repeat (STR) typing. Mitochondrial DNA was only obtained by performing PCR of very short fragments ( approximately 100 bp), indicating high DNA degradation. Different low frequency hypervariable region I haplotypes were obtained from each tissue section (normal tissue section haplotype: 16224C, 16234T, 16311C, 16356C; cancer tissue section haplotype: 16256T, 16270T, 16293G). Only the normal tissue section haplotype matched that obtained from the patient's blood sample, indicating that the cancer tissue section originated from an unknown patient. These results supported the hypothesis of sample mix up during block processing or slide preparation by a carryover mechanism. Mitochondrial genetic typing is recommended to exclude the possibility of carryover artefacts when low DNA content and high degradation compromise conventional STR typing.

Artifacts↗
PubMed2004

Limits for the central production of Theta+ and Xi(--)pentaquarks in 920-GeV pA collisions.

We have searched for Theta+(1540) and Xi(--)(1862) pentaquark candidates in proton-induced reactions on C, Ti, and W targets at midrapidity and square root of s = 41.6 GeV. In 2 x 10(8) inelastic events we find no evidence for narrow (sigma approximately 5 MeV) signals in the Theta+ --> pK0(S) and Xi(--) --> Xi- pi- channels; our 95% C.L. upper limits (UL) for the inclusive production cross section times branching fraction B dsigma/dy/(y approximately 0) are (4-16) mub/N for a Theta+ mass between 1521 and 1555 MeV, and 2.5 mub/N for the Xi(--). The UL of the yield ratio of Theta+/Lambda(1520) < (3-12)% is significantly lower than model predictions. Our UL of B Xi(--)/Xi(1530)0 < 4% is at variance with the results that have provided the first evidence for the Xi(--).

Journal Article↗
PubMed2004

17 STR data (AmpF/STR Identifiler and Powerplex 16 System) from Cabinda (Angola).

Allele frequencies for seventeen STRs included in the AmpF/STR Identifiler (CSF1PO, D2S1338, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D19S433, D21S11, FGA, TH01, TPOX, and VWA) and Powerplex 16 System (CSF1PO, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, FGA, Penta D, Penta E, TH01, TPOX, and VWA) were estimated from a sample of 110 unrelated individuals from Cabinda, Angola. Comparative analyses between our population data and other African databases, namely Promega's African-Americans, AB Applied Biosystems African-Americans and five other population samples gathered from the literature are also presented.

Angola↗
PubMed2004

Pattern of mtDNA variation in three populations from São Tomé e Príncipe.

We have analysed the matrilineal genetic composition of three self-reported ethnic groups from São Tomé e Príncipe (Gulf of Guinea), an African archipelago whose settlement begun in the late fifteenth century. Sequence data from the hypervariable segments I (HVS-I) and II (HVS-II) were obtained for 30 Angolares, 35 Forros and 38 Tongas. The repertory of mtDNA lineages in São Tomé e Príncipe denoted a fully African maternal pool, primarily arisen from a Central/Southwestern substratum. The absence of any lineages of putative European descent means that the European impact at the mitochondrial pool was virtually nil. Angolares showed a clear reduction of mtDNA diversity and a slight genetic differentiation relative to Tongas or Forros, whereas the latter two groups did not present any signs of genetic boundaries between each other. The data obtained here reinforce the depiction of genetic substructuring in São Tomé e Príncipe previously derived from Y-chromosome STRs. In addition, the crossing of mtDNA and Y-STR information led to the inference that the female mediated gene flow within the archipelago was less restricted than the male, a pattern that could be framed in the cultural traditions and socio-historical interactions among the groups.

Africa↗
PubMed2004

Tracing the origin of the most common thiopurine methyltransferase (TPMT) variants: preliminary data from the patterns of haplotypic association with two CA repeats.

Thiopurine methyltransferase (TPMT) is an essential enzyme for normal metabolism of thiopurine drugs. In humans TPMT activity is largely dependent upon genetic variation at the TPMT locus, with TPMT*3A and TPMT*3C being the most frequent mutant alleles associated with reduced activity. TPMT*3C is a widespread allele reaching the highest frequencies in Africans, whereas TPMT*3A is virtually restricted to Caucasian descendent populations. To estimate the time of origin of these two alleles, we analyzed the levels of diversity at two CA repeats flanking the TPMT gene. In accordance to its pattern of geographical distribution, the study of the decay in linkage disequilibrium over time indicated that TPMT*3A was the younger allele. The estimated age was 5700 years, which coincides with the Neolithic, a period characterized by major population expansion that could have been responsible for the spread of TPMT*3A from its place of origin, maybe a western Eurasian population. TPMT*3C was found to have arisen earlier, roughly 14000 years ago, which could explain the worldwide dispersal of TPMT*3C.

Age Distribution↗
PubMed2002

Extending STR markers in Y chromosome haplotypes.

Two multiplex reactions were developed to amplify 16 Y-STRs (DYS19, DYS385, DYS389 I and II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, GATA A7.1, GATA A7.2, GATA A10, GATA C4, GATA H4). Here we extend previous population studies done in a sample from northern Portugal for the GATA A7.1, GATA A7.2, GATA C4 and GATA H4 loci. A total of 199 different haplotypes identified by the 16 Y-STR markers were observed in a sample of 208 male individuals, of which 190 were unique and 9 were found twice. The overall haplotype diversity was 0.9996. The haplotype diversity of the Y-STR set composed of the 8 new markers is higher than the Y-STR core set included in the Y-STR haplotype reference database. Sequence structure of new alleles for GATA C4 and GATA H4 is reported. The usefulness of the inclusion of this new set of Y-STRs in forensic casework was also assessed. The increase in haplotype diversity with the addition of any new Y-STR marker to the 8 Y-STR core set is dependent not only on the gene diversity (positively) but also (negatively) on the degree of gametic association between the markers and the haplotypes previously defined. For instance, in our sample the addition of the DYS437, DYS438 and GATA A7.2 to a 13-locus set increased haplotype diversity only by 0.0001.

Base Sequence↗
PubMed2002

Genetic diversity of Y-specific STRs in chimpanzees (Pan troglodytes).

Using the primers described for humans, sequences for 11 Y-specific microsatellites (DYS434, DYS435, DYS436, DYS437, DYS438, DYS439, GATA A10, A7.1, A7.2, C4, and H4 [Gusmão et al., in press]), previously described in 10 male chimpanzees (Pan troglodytes), were confirmed in nine additional male chimpanzees. Sequences for nine additional microsatellites (DYS19, DYS385I and II, DYS389I and II, DYS390, DYS391, DYS392, and DYS393) were determined in all 19 male chimpanzees; homology to human Y-Short Tandem Repeat (STRs) was confirmed by sequencing. Good amplification results were not obtained for DYS19 and DYS385I/II. Two amplicons were obtained for DYS389I/II, but in contrast to humans, the larger fragment was not Y-specific. Moreover, no polymorphism was observed for DYS434, DYS435, or GATA A10. Consequently, these eight STRs were eliminated from further analyses, and haplotype and allele frequencies were estimated for the remaining 12 STRs. A high haplotype diversity value was found (1.000 +/- 0.017), demonstrating the usefulness and informative power of these Y-STRs for future studies on chimpanzee population genetics.

Amino Acid Sequence↗