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Rene J Herrera

Publications and source records attributed to Rene J Herrera.

10 recordsLinked to original sources
PubMed2003

Inferring recent human phylogenies using forensic STR technology.

STR loci are characterized by extremely high mutation rates and thus, high levels of length polymorphism both within and among populations. In addition, much of the observed variation is believed to be nearly selectively neutral. Because of these features, STRs are ideal markers for genetic mapping, intra-species phylogenetic reconstructions and forensic analysis. In the present study, we investigate the application of five STR loci (CS1PO, TH01, TPOX, FGA and vWA) routinely used in forensic analysis for delineating the phylogenetic relationships of 10 human populations representing the three major racial groups (African-Caribbean, Croatian from the island of Hvar, East Asian, Han Chinese, Italian, Japanese, Portuguese, UK Caucasian, US Caucasian and Zimbabwe). The resulting tree topology exhibited strong geographic and racial partitioning consistent with that obtained with mtDNA haplotypes, Y-chromosome markers, SNPs, PAIs (polymorphic Alu insertions) as well as classic genetic polymorphisms. These findings suggest that forensic STR loci may be particularly powerful tools and provide the necessary fine resolution for the reconstruction of recent human evolutionary history.

DNA Fingerprinting↗
PubMed2003

Two problematic human polymorphic Alu insertions.

Analysis of two previously described polymorphic Alu insertions (Sb19.3 and NBC3) in world-wide human populations generated genotypic frequencies grossly in violation of Hardy-Weinberg equilibrium expectations. GenBank searches at the National Center for Biotechnology Information (NCBI) and sequencing analyses revealed that samples homozygous for the Sb19.3 Alu insertion amplify a band indistinguishable in size to the lack of insertion amplicon, corresponding to a paralogous locus on chromosome 4. This locus displays a very similar sequence (84%) to that flanking the Sb19.3 Alu insertion located at chromosome 19. Moreover, we have determined that NBC3, a different Alu insertion, is not located in the pseudoautosomal region of the Y-chromosome, as previously reported, but in position Yq11.2. Also, the band that mimics the lack of insertion amplicon corresponds to a paralogous locus located at chromosome X with a similarity of 92% to the sequence flanking the NBC3 Alu insertion. Finally, the utilization of newly designed primers avoided amplification from the paralogous loci and allowed a reliable assignation of genotypes for both loci. Unlike previously reported, using our new primers the Y-specific locus NBC3 was found not to be polymorphic in the populations analyzed.

Alu Elements↗
PubMed2002

Single-nucleotide polymorphism in repetitive sequences of the human deleted in azoospermia complex.

A simple and inexpensive single-nucleotide polymorphism (SNP) analysis procedure is described that uses the Fotodyne Analyst System equipped with the Gel-Pro Analysis software to compare the relative fluorescent intensity of ethidium bromide stained and MboI restricted amplicons from male individuals. The different intensity ratios reflect the ratio of repetitive elements with and without an MboI restriction enzyme site. The polymerase chain reaction (PCR) products represent a reiterated sequence within the Y-linked deleted in azoospermia (DAZ) complex involved in male fertility in humans. This procedure was utilized to determine the ratio of MboI(+) and MboI(-) repetitive sequences in 32 male individuals from two human populations, the Buryat from Mongolia and the Mayan from Yucatan. The proportion of wildtype to mutant amplicons was found to vary from 0 to 100% among individuals. This technique is well suited for large-scale analysis of the locus investigated in this manuscript and other similar polymorphisms. This approach may contribute to the study of recent human evolution based on Y-chromosome analysis as well as medical and developmental issues concerning the significance of these repetitive elements in male infertility.

Base Sequence↗
PubMed2002

Phylogenetics of worldwide human populations as determined by polymorphic Alu insertions.

Alu elements, the largest family of interspersed repeats, mobilize throughout the genomes of primates by retroposition. Alu are present in humans in an excess of 500 000 copies per haploid genome. Since some of the insertion alleles have not reached fixation, they remain polymorphic and can be used as biallelic DNA marker systems in investigations of human evolution. In this study, six polymorphic Alu insertional (PAI) loci were used as genetic markers. These markers are thought to be selectively neutral. The presence of these six PAIs was determined by a polymerase chain reaction (PCR)-based assay in 1646 individuals from 47 populations from around the world. Examination of the populations by plotting the first and second principal components, shows the expected segregation of populations according to geographical vicinity and established ethnic affinities. Centroid analysis demonstrated that sub-Sahara populations have experienced higher than average gene flow and/or represent larger populations as compared to groups in other parts of the globe and especially to known inbreed populations. This is consistent with greater heterogeneity and diversity expected of source groups. In addition, maximum likelihood (ML) analyses were performed with these 47 populations and a hypothetical ancestral group lacking the insertion in all six loci. Analysis of our data supports the Out of Africa hypothesis. African populations and admixed groups of African descent formed a single monophyletic group with a basal placement on the tree, which grouped closest to the hypothetical ancestor.

Alu Elements↗
PubMed2002

On the genetic uniqueness of the Ami aborigines of Formosa.

In the attempt to reconstruct the prehistory of Pacific and Indian Ocean populations, Taiwan's aborigines appear to be of particular interest. Linguistic and archeological evidence indicates that the dispersal of Austronesian speakers throughout the islands of Oceania and Southeast Asia may have originated from Taiwan about 5,000 years ago. The Ami are Taiwan's largest aboriginal group. Here, we report on six polymorphic point mutation loci in Ami individuals and compare allelic frequencies to worldwide populations. In order to examine the genetic characteristics and relationships of the Ami aborigines, we used the allelic frequency data to generate expected heterozygosities, power of discrimination values, maximum likelihood phylogenetic trees, principal component maps, and centroid gene flow plots. These analyses argue for the genetic isolation and uniqueness of the Ami people. Data supportive of limited gene flow and/or small population size, as well as genetic similarities to Native Americans, were observed.

Biological Evolution↗
PubMed2002

Functional study of a recombinant form of human LHbeta-subunit variant carrying the Gly(102)Ser mutation found in Asian populations.

Genetic variants of human LH caused by amino acid replacements in the beta-subunit have been demonstrated to affect reproductive function. Occurrence of a G(1502)A substitution in the LHbeta gene leading to Gly(102)Ser replacement of the LHbeta protein has been found to be associated with infertility in the Singapore Chinese population. In the present study, a search for this LHbeta allele from 383 DNA samples from different continents, using a PCR-based strategy, demonstrated its total absence in these populations. Functional properties of the variant (V) (Gly(102)Ser substitution) LHbeta subunit were assessed using a recombinant (r) form of V-LH produced in HEK293 cells, in comparison with wild-type (WT) LH or hCG. The synthesized V-LH was purified by a single step of immunoaffinity chromatography, and it had a molecular weight of 30 kDa as determined by SDS-PAGE. The affinities of the WT-hCG and rV-LH in mouse Leydig tumour (mLT-1) cell LH receptor binding were similar, with K(d) values of 0.140 +/- 0.03 and 0.156 +/- 0.01 nmol/l respectively. Likewise, the effects of WT- and V-rLH preparations on mLT-1 cell cAMP and progesterone production were concentration-dependent and with similar biopotencies. In addition, HEK293 cells expressing the human LH receptor documented similar dose-dependent increases in inositol phosphate production by the two rLH forms. In conclusion, these findings demonstrate that Gly(102)Ser mutation of the LHbeta gene does not affect receptor binding and bioactivity of the hormone, when tested in vitro.

Animals↗
PubMed2002

A novel Ala(-3)Thr mutation in the signal peptide of human luteinizing hormone beta-subunit: potentiation of the inositol phosphate signalling pathway and attenuation of the adenylate cyclase pathway by recombinant variant hormone.

Upon screening for polymorphisms in the human luteinizing hormone beta-subunit (LH beta) gene, we discovered a novel mutation in the LH beta signal peptide with functional consequences for signal transduction in mouse Leydig tumour cells (mLTC-1). This G(52)A point mutation in exon 2 of the LH beta gene, detected in heterozygous form in several normal DNA samples, caused an Ala(-3)Thr amino acid substitution. Recombinant forms of wild-type (WT) and Ala(-3)Thr variant (V) LH were produced in human embryonic kidney (HEK) 293 cells and purified. The immunoreactivities of the recombinant LH were determined by immunofluorometric assays and in-vitro bioactivities in mLTC-1 cells were assessed by using cAMP, progesterone and inositol trisphosphate (IP(3)), and activation of mitogen-activated protein kinase (MAPK) as end-points. Whereas both LH forms stimulated progesterone production and MAPK in similar fashion, WT-LH was more potent in stimulating cAMP, and V-LH was more potent in stimulating IP(3) generation. Both LH forms bound to LH receptors with similar affinities. No evidence was found for influence of the signal peptide mutation on efficacy of alpha- and beta-subunit dimerization. Sequencing of the recombinant V-LH beta protein also revealed that the mutation did not interfere with signal peptide cleavage. In summary, the present findings indicate that the Ala(-3)Thr mutation in the LH beta-subunit signal peptide has functional consequences, in the form of dissociation of stimulatory potency for different signal transduction pathways in vitro.

Adenylyl Cyclases↗
PubMed2002

Single-nucleotide variant in multiple copies of a deleted in azoospermia (DAZ) sequence - a human Y chromosome quantitative polymorphism.

The evolution of the deleted in azoospermia (DAZ) gene family supports prevalent theories on the origin and development of sex chromosomes and sexual dimorphism. The ancestral DAZL gene in human chromosome 3 is known to be involved in germline development of both males and females. The available phylogenetic data suggest that some time after the divergence of the New World and Old World monkey lineages, the DAZL gene, which is found in all mammals, was copied to the Y chromosome of an ancestor to the Old World monkeys, but not New World monkeys. In modern man, the Y-linked DAZ gene complex is located on the distal part of the q arm. It is thought that after being copied to the Y chromosome, and after the divergence of the human and great ape lineages, the DAZ gene in the former underwent internal rearrangements. This included tandem duplications as well as a T > C transition altering an MboI restriction enzyme site in a duplicated sequence. In this study, we report on the ratios of MboI-/MboI+ variant sequences in individuals from seven worldwide human populations (Basque, Benin, Egypt, Formosa, Kungurtug, Oman and Rwanda) in the DAZ complex. The ratio of PCR MboI- and MboI+ amplicons can be used to characterize individuals and populations. Our results show a nonrandom distribution of MboI-/MboI+ sequence ratios in all populations examined, as well as significant differences in ratios between populations when compared pairwise. The multiple ratios imply that there have been more than one recent reorganization events at this locus. Considering the dynamic nature of this locus and its involvement in male fertility, we investigated the extent and distribution of this polymorphism.

Deleted in Azoospermia 1 Protein↗