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F Figueroa

Publications and source records attributed to F Figueroa.

At least 55 records · Page 3Linked to original sources
PubMed1994

Alu elements of the primate major histocompatibility complex.

The chromosomal region constituting the major histocompatibility complex (MHC) has undergone complex evolution that is often difficult to decipher. An important aid in the elucidation of the MHC evolution is the presence of Alu elements (repeats) which serve as markers for tracing chromosomal rearrangements. As the first step toward the establishment of sets of evolutionary markers for the MHC, Alu elements present in selected MHC haplotypes of the human species, the gorilla, and the chimpanzee were identified. Restriction fragments of cosmid clones from the libraries of the three species were hybridized with Alu-specific probes, Alu elements were amplified by the polymerase chain reaction, and the amplification products were sequenced. In some cases, sequences of the regions flanking the Alu elements were also obtained. Altogether, 31 new Alu elements were identified, representing six Alu subfamilies. The average density of Alu elements in the MHC is one element per four kilobases (kb) of sequence. Alu elements have apparently been inserted steadily into the MHC over the last 65 million years (my). On average, one Alu element is inserted into the primate MHC every 4 my. Analysis of the human DR3 haplotype supports its origin by duplication from an ancestral haplotype consisting of DRB1 and DRB2 genes. The sharing of an old Alu element by the DRB1 and DRB2 genes, in turn, supports their divergence from a common ancestor more than 55 my ago.

Animals↗
PubMed1994

Origin of the North American house mouse.

The house mouse, Mus domesticus, was introduced to the American continent in the post-Columbian era. We have used mouse chromosome 17 DNA probes to trace the origin of the wild house mice on the East Coast of the United States. Of the four probes used, one in particular proved to be informative in this regard. The D17Tu20 probe defines a polymorphism at a locus telomeric of the H-2 complex. TaqI restriction enzyme digests of genomic DNA blotted and hybridized with the D17Tu20 probe revealed the existence of restriction fragments shared by mice from the Atlantic coast of England, France, and the United States but absent in all other tested populations sampled from different parts of the world. This unique polymorphic pattern apparently arose by the loss of two restriction sites in the population on the coast of Brittany. The mutations then presumably spread to England, and from there to the United States. Since the mutations are also present in mice from Florida, English (rather than Spanish) mouse populations may have been either the sole or the main source of immigrants to the eastern United States. This conclusion is also supported by data obtained with the other probes. Presence of the D17Tu20 mutations in some of the laboratory strains indicates that American wild mice contributed to the gene pool of the inbred strains. We postulate that the colonization of North America by English wild mice began in the second half of the seventeenth century.

Animals↗
PubMed1993

Zebrafish Mhc class II alpha chain-encoding genes: polymorphism, expression, and function.

Its small size and short generation time renders the zebrafish (Brachydanio rerio) an ideal vertebrate for immunological research involving large populations. A prerequisite for this is the identification of the molecules critical for an immune response in this species. In earlier studies, we cloned the zebrafish genes coding for the beta chains of the class I and class II major histocompatibility complex (Mhc) molecules. Here, we describe the cloning of the zebrafish alpha chain-encoding class II gene, which represents the first identification of a class II A gene in teleost fishes. The gene, which is less than 3 kilobases (kb) distant from one of the beta chain-encoding genes, is approximately 1.2 kb long and consists of four exons interrupted by very short (< 200 base pairs) introns. Its organization is similar to that of the mammalian class II A genes, but its sequence differs greatly from the sequence of the latter (36% sequence similarity). Among the most conserved parts is the promoter region, which contains X, Y, and TATA boxes with high sequence similarity to the corresponding mammalian boxes. The observed striking conservation of the promoter region suggests that the regulatory system of the class II genes was established more than 400 million years ago and has, principally, remained the same ever since. Like the DMA, but unlike all other mammalian class II A genes, the zebrafish gene codes for two cysteine residues which might potentially be involved in the formation of a disulfide bond in the alpha 1 domain. The primary transcript of the gene is 1196 nucleotides long and contains 708 nucleotides of coding sequence. The gene is expressed in tissues with a high content of lymphoid/myeloid cells (spleen, pronephros, hepatopancreas, and intestine). The analyzed genomic and cDNA sequences are probably derived from different loci (their overall sequence similarity in the coding region is 73% and their 3' untranslated regions are highly divergent from each other). The genes are apparently functional. Comparison of genes from different zebrafish populations reveals high exon 2 variability concentrated in positions coding for the putative peptide-binding region. Phylogenetic analysis suggests that the zebrafish class II A genes stem from a different ancestor than the mammalian class II A genes and the recently cloned shark class II A gene.

Amino Acid Sequence↗
PubMed1993

Cloning of the beta 2-microglobulin gene in the zebrafish.

The beta 2-microglobulin (beta 2m) is a protein found in the serum in a free form and on the cell surface in a form noncovalently associated with the alpha chain of the class I major histocompatibility complex (Mhc) molecules. In mammals, the beta 2m-encoding gene (B2m) is found on a chromosome different from the Mhc proper. We have isolated and characterized the B2m gene of the zebrafish, Brachydanio rerio, family Cyprinidae. We obtained both cDNA and genomic clones of the Brre-B2m gene. The cDNA clones contained the entire coding sequence, the entire 3' untranslated (UT) region, and at least part of the 5'UT region. The genomic clone contained the entire Brre-B2m gene. The coding sequence specifies 97 amino acid residues of the mature protein so that the zebrafish beta 2m is two residues shorter than human and one residue shorter than cattle, fowl, or turkey beta 2m (codons at positions 85 and 86 have been deleted in the Brre-B2m gene). The amino acid and nucleotide sequence similarities between zebrafish and human beta 2m (B2m) are 45% and 59%, respectively. Approximately 24% of the positions are invariant and an additional 9% show only conservative substitutions in comparisons which include all known beta 2m sequences (fish, avian, and mammalian). Most of the conserved positions are in the beta strands (some 47% of the beta-strand positions are conserved in the three vertebrate classes). The Brre-B2m gene consists of four exons separated by three introns. All of the introns are considerably shorter than the corresponding introns in the mammalian B2m genes. The coding sequences of the cDNA and the genomic clones are almost identical but the sequences of the 3'UT regions differ at 1.7% of the sites, suggesting that the genes borne by these clones might have diverged at least 0.7 million years (my) ago. In contrast to the human B2m gene, the Brre-B2m gene shows no bias in the distribution of the CpG dinucleotides: the dinucleotides are distributed evenly along the entire available sequence. The haploid genome of the zebrafish contains only one copy of the B2m gene.

Amino Acid Sequence↗
PubMed1993

Conservative evolution of the Mbc-DP region in anthropoid primates.

To determine the organization of the DP region in the Mbc of anthropoid primates, we constructed contig maps from cosmid clones of the chimpanzee and orangutan, representatives of the infraorder Catarrhini, as well as of the cotton-top tamarin, a representative of the infraorder Platyrrhini. We found the maps to be remarkably similar to each other and to the previously published map of the human DP region. In each of the four species, the DP region consists of four loci arranged in the same order (DPB2 . . . DPA2 . . . DPB1 . . . DPA1) and in the same transcriptional orientation (tail-to-tail). The regions in the four species are of approximately the same length and many of the restriction sites are shared between species. The inserts of most Alu elements, of a ribosomal protein pseudogene, and of an IgC epsilon-like pseudogene are found in corresponding positions in all four species. The data indicate that the human-type organization of the DP region was established before the divergence of the Catarrhini and Platyrrhini lines more than 37 million years ago and that it has remained principally intact since that time. This conservation of the DP region is in striking contrast to the evolutionary instability of certain other Mbc regions, in particular those occupied by the DRB or C4 and CYP21 loci. We interpret the stability of the DP region as an indication that the region is being phased out functionally.

Animals↗
PubMed1993

Dating the primigenial C4-CYP21 duplication in primates.

C4 and CYP21 are two adjacent, but functionally unrelated genes residing in the middle of the mammalian major histocompatibility complex (Mhc). The C4 gene codes for the fourth component of the complement cascade, whereas the CYP21 gene specifies an enzyme (cytochrome P450c21) of the glucocorticoid and mineralocorticoid pathways. The genes occur frequently in multiple copies on a single chromosome arranged in the order C4 ... CYP21 ... C4 ... CYP21. The unit of duplication (a module) is the C4-CYP21 gene pair. We sequenced the flanking regions of the C4-CYP21 modules and the intermodular regions of the chimpanzee, gorilla, and orangutan, as well as the intermodular region of an Old World monkey, the pigtail macaque. By aligning the sequences, we could identify the duplication breakpoints in these species. The breakpoint turned out to be at exactly the same position as that found previously in humans. The sequences flanking paralogous genes in the same species were found to be more similar to one another than sequences flanking orthologous genes in different species. We interpret these results as indicating that the original (primigenial) duplication occurred before the separation of apes from Old World monkeys more than 23 million years ago. The nature of the sequence at the breakpoint suggests that the duplication occurred by nonhomologous recombination. Since then, the C4-CYP21 haplotypes have been expanding and contracting by homologous crossing over which has homogenized the sequences in each species.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Different modes of Mhc evolution in primates.

The human major histocompatibility complex (Mhc) is a chromosomal segment approximately 4 million bp long that contains > or = 84 genes. Some of these genes code for the class I and class II molecules, while the remaining genes code for complement components, cytochrome P450, tumor necrosis factor, and many other, unrelated proteins. We demonstrate on three examples (DP, C4-CYP21, and DRB) that different regions of the Mhc have different evolutionary histories. The organization of the DP region, which in humans contains four genes, was established in the ancestral Anthropoidea or earlier and has not changed since. The duplication that generated the two C4-CYP21 modules occurred in the ancestral Catarrhini or earlier, but the region has been undergoing periodic homogenizations via unequal crossing-over, which make paralogous genes in the same species more similar to each other than to orthologous genes of different species. The eight or nine genes of the DRB region were also generated in the ancestral Catarrhini, but the region has since been subject to frequent rearrangements, which generated various DRB haplotypes. Not only the alleles but, in part, also the haplotype polymorphism is evolving transspecifically. The DRB region of the Platyrrhini has an origin different from that of the Catarrhini. The picture emerging from these studies is that of both stability in some regions of the Mhc and tremendous evolutionary instability in other regions.

Animals↗
PubMed1993

[Pharmacological modification of prolactinemia. Effects on cellular immune function in normal subjects].

Prolactin markedly influences cellular and humoral immunity in animals, but there is little information on its role in men. The aim of this work was to study the immune effects of pharmacological modification of prolactin levels in 5 healthy individuals. Peripheral blood mononuclear cell proliferative response to mitogens and antigens, interleukin-2 (IL-2) production, soluble and membrane IL-2 receptor expression in peripheral blood mononuclear cells and serum soluble IL-2 receptors were successively measured during normoprolactinemia, during bromocriptine induced hypoprolactinemia and during metoclopramide induced hyperprolactinemia. There was a significant increase in cellular proliferation during hypoprolactinemia when compared with hyperprolactinemia. No concomitant changes in soluble or membrane receptor expression or IL-2 production were observed. It is concluded that lymphocyte proliferative response to mitogens is dependent on prolactin levels in man and that this effects is not mediated by IL-2 or its receptors. These results may be potentially relevant in clinic since changes in serum prolactin have been described in different autoimmune diseases.

Adult↗
PubMed1992

Major histocompatibility complex class II genes of zebrafish.

Twenty cDNA clones derived from beta-chain-encoding class II genes of the zebrafish (Brachydanio rerio) major histocompatibility complex (MHC) have been sequenced. They fall into three groups identifying three loci of expressed genes. The length and organization of these genes are similar to those of their mammalian homologs. Amplification by polymerase chain reaction and sequencing of genomic DNA from zebrafish collected at different locations in India indicate the existence of a fourth group of sequences (fourth locus). A high degree of polymorphism at the B. rerio MHC loci and concentration of variability to the putative peptide-binding region of the beta 1-domain-encoding part of the gene are also indicated. Large genetic distances between alleles suggest trans-specific evolution of fish MHC polymorphism. Zebrafish genes appear to be derived from a different ancestor than the various class II gene families of other vertebrates. In spite of great sequence divergence between fish and mammalian MHC genes, there seems to be a striking conservation in their overall organization.

Animals↗
PubMed1992

The evolutionary origin of the HLA-DR3 haplotype.

The human HLA-DR3 haplotype consists of two functional genes (DRB1*03 and DRB3*01) and one pseudogene (DRB2), arranged in the order DRB1...DRB2...DRB3 on the chromosome. To shed light on the origin of the haplotype, we sequenced 1480 nucleotides of the HLA-DRB2 gene and long stretches of two other genes, Gogo-DRB2 from a gorilla, "Sylvia" and Patr-DRB2 from a chimpanzee, "Hugo". All three sequences (HLA-DRB2, Gogo-DRB2, Patr-DRB2) are pseudogenes. The HLA-DRB2 and Gogo-DRB2 pseudogenes lack exon 2 and contain a twenty-nucleotide deletion in exon 3, which destroys the correct translational reading frame and obliterates the highly conserved cysteine residue at position 173. The Patr-DRB2 pseudogene lacks exons 1 and 2; it does not contain the twenty-nucleotide deletion, but does contain a characteristic duplication of that part of exon 6 which codes for the last four amino acid residues of the cytoplasmic region. When the nucleotide sequences of these three genes are compared to those of all other known DRB genes, the HLA-DRB2 is seen as most closely related to Gogo-DRB2, indicating orthologous relationship between the two sequences. The Patr-DRB2 gene is more distantly related to these two DRB2 genes and whether it is orthologous to them is uncertain. The three genes are in turn most closely related to HLA-DRBVI (the pseudogene of the DR2 haplotype) and Patr-DRB6 (another pseudogene of the Hugo haplotype), followed by HLA-DRB4 (the functional but nonpolymorphic gene of the DR4 haplotype). These relationships suggest that these six genes evolved from a common ancestor which existed before the separation of the human, gorilla, and chimpanzee lineages. The DRB2 and DRB6 have apparently been pseudogenes for at least six million years (myr). In the human and the gorilla haplotype, the DRB2 pseudogene is flanked on each side by what appear to be related genes. Apparently, the DR3 haplotype has existed in its present form for more than six myr.

Animals↗
PubMed1992

C4 genes of the chimpanzee, gorilla, and orang-utan: evidence for extensive homogenization.

The human complement component 4 is encoded in two genes, C4A and C4B, residing between the class I and class II genes of the major histocompatibility complex. The C4A and C4B molecules differ in their biological activity, the former binding more efficiently to proteins than to carbohydrates while for the latter, the opposite holds true. To shed light on the origin of the C4 genes we isolated cosmid clones bearing the C4 genes of a chimpanzee, a gorilla, and an orang-utan. From the clones, we isolated the fragments coding for the C4d part of the gene (exons and introns) and sequenced them. Altogether we sequenced eight gene fragments: three chimpanzee (Patr-C4-1*01, Patr-C4-1*02, Patr-C4-2*01), two gorilla (Gogo-C4-1*01, Gogo-C4-2*01), and three orang-utan (Popy-C4-1*01, Popy-C4-2*01, Popy-C4-3*01). Comparison of the sequences with each other and with human C4 sequences revealed that in the region believed to be responsible for the functional difference between the C4A and C4B proteins the C4A genes of the different species fell into one group and the C4B genes fell into another. In the rest of the sequence, however, the C4A and C4B genes of each species resembled each other more than they did C4 genes of other species. These results are interpreted as suggesting extensive homogenization (concerted evolution) of the C4 genes in each species, most likely by repeated unequal, homologous, intragenic crossing-over.

Animals↗
PubMed1992

Polymorphisms distinguishing different mouse species and t haplotypes.

Three anonymous chromosome 17 DNA markers, D17Tu36, D17Tu43, and D17Le66B, differentiate between house mouse species and/or between t chromosomes. The D17Tu36 probe, which maps near the Fu locus and to the In(17)4 on t chromosomes, identifies at least 15 haplotypes, each haplotype characterized by a particular combination of DNA fragments obtained after digestion with the Taq I restriction endonuclease. Ten of these haplotypes occur in Mus domesticus, while the remaining five occur in M. musculus. In each of these two species, one haplotype is borne by t chromosomes while the other haplotypes are present on non-t chromosomes. The D17Tu43 probe, which maps near the D17Leh122 locus and to the In(17)3 on t chromosomes, also identifies at least 15 haplotypes in Taq I DNA digests, of which nine occur in M. domesticus and six in M. musculus. One of the nine M. domesticus haplotypes is borne by t chromosomes, the other haplotypes are borne by non-t chromosomes; two of the six M. musculus haplotypes are borne by t chromosomes and the remaining four by non-t chromosomes. Some of the D17Tu43 haplotypes are widely distributed in a given species, while others appear to be population-specific. Exceptions to species-specificity are found only in a few mice captured near the M. domesticus-M. musculus hybrid zone or in t chromosomes that appear to be of hybrid origin. The D17Leh66B probe, which maps to the In(17)2, distinguishes three haplotypes of M. domesticus-derived t chromosomes and one haplotype of M. musculus-derived t chromosomes. Because of these characteristics, the three markers are well suited for the study of mouse population genetics in general and of t chromosome population genetics in particular. A preliminary survey of wild M. domesticus and M. musculus populations has not uncovered any evidence of widespread introgression of genes from one species to the other; possible minor introgressions were found only in the vicinity of the hybrid zone. Typing of inbred strains has revealed the contribution of only M. domesticus DNA to the chromosome 17 of the laboratory mouse.

Animals↗
PubMed1992

Major-histocompatibility-complex DRB genes of a New-World monkey, the cottontop tamarin (Saguinus oedipus).

The DRB region of the human and great-ape major histocompatibility complex displays not only gene but also haplotype polymorphism. The number of genes in the human DRB region can vary from one to four, and even greater variability exists among the DRB haplotypes of chimpanzees, gorillas, and orangutans. Accumulating evidence indicates that, like gene polymorphism, part of the haplotype polymorphism predates speciation. In an effort to determine when the gene haplotype polymorphisms emerged in the primate lineage, we sequenced three cDNA clones of the New-World monkey, the cottontop tamarin (Saguinus oedipus). We could identify two DRB loci in this species, one (Saoe-DRB1) occupied by apparently functional alleles (*0101 and *0102) which differ by only two nucleotide substitutions and the other (Saoe-DRB2) occupied by an apparent pseudogene. The Saoe-DRB2 gene contains an extra sequence derived from the 3' portion of exon 2 and placed 5' to this exon. This sequence contains a stop codon which makes the translation of the bulk of the Saoe-DRB2 gene unlikely. Preliminary Southern blot hybridization analysis with probes derived from these two genes suggests that both the DRB gene polymorphism and the haplotype polymorphism in the cottontop tamarin may be low. In most individuals the DRB region of this species probably consists of three genes. Comparisons of the Saoe-DRB sequences with those of other primates suggest that probably all of the DRB genes found until now in the Catarrhini were derived from a common ancestor after the separation of the Catarrhini and Platyrrhini lineages. The extant DRB gene and haplotype polymorphism may therefore have been founded in the mid-Oligocene some 33 Mya.

Amino Acid Sequence↗
PubMed1992

Anticardiolipin antibodies in acute rheumatic fever.

Recent reports describe the association of antiphospholipid antibodies (aPL) with chorea or severe heart valve lesions in systemic lupus erythematosus, lupus-like disease, or the primary antiphospholipid antibody syndrome. We conducted a case series and a case-control investigation of patients with rheumatic fever with Sydenham chorea or other manifestations of rheumatic fever for anticardiolipin antibodies (aCL) during the acute attack and disease remission. Eighty percent of patients were positive for aCL during the rheumatic fever attack vs 40% when inactive (p = 0.035); IgG and IgM aCL increased significantly with disease activity. Individuals with or without Sydenham chorea were equally positive for aCL (76 and 83%, respectively). A significant association was found between IgM aCL and carditis: All patients with valvulitis had IgM aCL (100%) vs 37% of patients without valvular involvement (p = 0.02). aPL may play a role in the pathogenesis of some clinical manifestations of acute rheumatic fever.

Acute Disease↗
PubMed1991

Origins of H-2 polymorphism in the house mouse. II. Characterization of a model population and evidence for heterozygous advantage.

Comparison of the rate of synonymous and nonsynonymous nucleotide substitutions suggests that certain regions of the functional H-2 genes, which are part of the mouse major histocompatibility complex (Mhc), are under strong positive selection pressure. Thus far, however, little evidence has been provided for the existence of such pressure in natural mouse populations. We have, therefore, initiated experiments designed to test the hypothesis of positive selection acting on H-2 loci. The experiments are being carried out on two natural mouse populations in Jerusalem, Israel. One population occupies a space of about 100 m2 in a chicken coop, the other lives in a nearby field in which "mouse stations" providing food and shelter have been set up. Extensive typing of these two populations revealed the presence of only four H-2 haplotypes. Mice in the two populations breed continually all year around, yet population size varies seasonally, with population maxima in winter and minima in summer. The population in the chicken coop contains a relatively stable nucleus which may be organized in demes with an excess of females over males and limited territorial mobility. The rest of the mice stay in the population for a short time only and then either die or emigrate. The field population is smaller and more loosely organized than the chicken-coop population, with demes probably forming only during population maxima. For the rest of the time breeding in this population is probably panmictic. At a population minimum in the summer of 1984, H-2 homozygotes happened to predominate over heterozygotes. This situation, however, lasted for a short time only and thereafter there was a continuous, statistically highly significant increase in the proportion of H-2 heterozygotes of one or two types. The increase occurred in both populations but was more apparent in the chicken-coop population. This observation provides the first experimental evidence that heterozygous advantage might be one of the mechanisms maintaining high H-2 polymorphism in natural populations of the house mouse.

Animals↗