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F Figueroa

Publications and source records attributed to F Figueroa.

At least 19 recordsLinked to original sources
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↗
PubMed1991

Primate DRB6 pseudogenes: clue to the evolutionary origin of the HLA-DR2 haplotype.

The HLA-DR2 haplotype contains three beta-chain encoding DRB genes and one alpha-chain encoding DRA gene. Of the three DRB genes, two are presumably functional (HLA-DRB1 and HLA-DRB5), whereas the third (HLA-DRBVI) is a pseudogene. A pseudogene closely related to HLA-DRBVI is present in the chimpanzee (Patr-DRB6) and in the gorilla (Gogo-DRB6). We sequenced the HLA-DRBVI and Patr-DRB6 pseudogenes (all exons and most of the introns), and compared the sequence to that of the Gogo-DRB6 gene (of which only the exon sequence is available). All three pseudogenes seem to lack exon 1 and contain other deletions responsible for shifts in the translational reading frame. At least the HLA-DRBVI pseudogene, however, seems to be transcribed nevertheless. The chimpanzee pseudogene contains two inserts in intron 2, one of which is an Alu repeat belonging to the Sb subfamily, while the other remains unidentified. These inserts are lacking in the human gene. A comparison with sequences published by other investigators revealed the presence of the HLA-DRBVI pseudogene also in the DR1 and DRw10 haplotypes. Measurements of genetic distances indicate DRB6 to be closely related to the DRB2 pseudogene and to the HLA-DRB4 functional gene. In humans, gorillas, and chimpanzees, the DRB6 pseudogene is associated with the same functional gene (DRB5) indicating that this linkage disequilibrium is at least six million years old and that DR2 is one of the oldest DR haplotypes in higher primates.

Animals↗
PubMed1991

Limits of the distal inversion in the t complex of the house mouse: evidence from linkage disequilibria.

The suppression of crossing-over and the consequent linkage disequilibrium of genetic markers within the t complex of the house mouse is caused by two large and two short inversions. The inversions encompass a region that is some 15 centiMorgans (cM) long in the homologous wild-type chromosome. The limits of the proximal inversions are reasonably well-defined, those of the distal inversions much less so. We have recently obtained seven new DNA markers (D17Tu) which in wild-type chromosomes map into the region presumably involved in the distal inversions of the t chromosomes. To find out whether the corresponding loci do indeed reside within the inversions, we have determined their variability among 26 complete and 12 partial t haplotypes. In addition, we also tested the same collection of t haplotypes for their variability at five D17Leh, Hba-ps4, Pim-1, and Crya-1 loci. The results suggest that the distal end of the most distal inversion lies between the loci D17Leh467 and D17Tu26. The proximal end of the large distal inversion was mapped to the region between the D17Tu43 and Hba-ps4 loci, but this assignment is rather ambiguous. The loci Pim-1, Crya-1, and the H-2 complex, which have been mapped between the Hba-ps4 and Grr within the large distal inversion, behave as if they recombine from time to time with their wild-type homologs.

Animals↗
PubMed1991

Isolation of 37 single-copy DNA probes from human chromosome 6 and physical mapping of 11 probes by in situ hybridization.

Fifty-five single-copy DNA probes were isolated from the library LL06NS01, which was constructed from a complete HindIII digest of a flow-sorted human chromosome 6. Because chromosomes from a human x Chinese hamster somatic cell hybrid were used as the starting material for the flow-sorting, the library could be expected to contain some contaminating Chinese hamster DNA as well as DNA from human chromosomes other than 6. Thirty-seven of the 55 probes, however, were shown to map to human chromosome 6 by Southern blot hybridization with DNA from a panel of somatic cell hybrids. Eleven of the probes were mapped further by in situ hybridization. Four probes were localized to the short arm of chromosome 6, six to the long arm, and one to the centromeric region.

Animals↗
PubMed1991

Low diversity of t haplotypes in the eastern form of the house mouse, Mus musculus L.

In previous studies, 13 different recessive embryonic lethal genes have been associated with t haplotypes in the wild mice of the species Mus domesticus. In this communication we have analyzed five populations of Mus musculus for the presence and identity of t haplotypes. The populations occupy geographically distant regions in the Soviet Union: Altai Mountains, western and eastern Siberia, Azerbaijan and Turkmenistan. No t haplotypes were found in mice from eastern Siberia. In the remaining four populations, t haplotypes occurred with frequencies ranging from 0.07 to 0.21. All the t haplotypes extracted from these populations and analyzed by the genetic complementation test were shown to carry the same lethal gene tcl-w73. In one population (that of western Siberia), another lethal gene (tcl-w5) was found to be present on the same chromosome as tcl-w73. This situation is in striking contrast to that found in the populations of the western form of the house mouse, M. domesticus. In the latter species, tcl-w73 has not been found at all and the different populations are characterized by the presence of several different lethal genes. The low diversity of t haplotypes in M. musculus is consistent with lower genetic variability of other traits and indicates a different origin and speciation mode compared to M. domesticus. Serological typing for H-2 antigenic determinants suggests that most, if not all, of the newly described t haplotypes might have arisen by recombination of tw73 from M. musculus with t haplotypes from M. domesticus either in the hybrid zone between the two species or in regions where the two species mixed accidentally.

Animals↗
PubMed1991

Mhc-DRB genes of the pigtail macaque (Macaca nemestrina): implications for the evolution of human DRB genes.

The DRB family of human class II major histocompatibility complex (Mhc) loci is unusual in that individuals differ in the number and combination of genes (haplotypes) they carry. Indications are that both the allelic and haplotype polymorphisms of the DRB loci predate speciation. Searching for the evolutionary origins of these polymorphisms, we have sequenced five DRB clones isolated from a cDNA library of a pigtail macaque (Macaca nemestrina) B lymphocyte line. The clones represent five different genes which we designate Mane-DRB*01-Mane-DRB*05. The genes appears to be approximately equidistant from each other, so that allelic relationships between them cannot be established on the basis of the sequence data alone. If positions coding for the peptide-binding region of the class II beta chains are eliminated from sequence comparisons, the Mane-DRB genes appear to be most closely related to the human (HLA) DRB1 genes of the DRw52 group. We interpret this finding to indicate that the ancestral gene of the DRw52 group of human DRB1 alleles separated from the rest of the HLA-DRB1 alleles before the separation of the Old World monkeys (Cercopithecoidea) from the apes (Hominoidea) in the early Oligocene. After this separation, the ancestral DRB1 gene of the DRw52 group duplicated in the Old World monkey lineage to give rise to genes at three loci at least, while in the ape lineage this gene may have remained single and diverged into a number of alleles instead. These findings suggest that some of the polymorphism currently present at the DRB1 locus is greater than 35 Myr old.

Alleles↗
PubMed1991

MHC class II genes of a marsupial, the red-necked wallaby (Macropus rufogriseus): identification of new gene families.

In placental mammals, the class II region of the major histocompatibility complex (Mhc) consists of several gene families which show orthologous relationships in the different species. As these families are not orthologous with the Mhc class II beta-chain-encoding gene families of birds, the different mammalian families must have diverged after the separation of birds and mammals approximately 250 Mya but before the radiation of placental mammals (60-80 Mya). To obtain further information about the origin of the class II genes in mammals, we studied the beta-chain-encoding genes of the wallaby as a representative of marsupials, which split from placental mammals approximately 125 Mya. Three beta-chain-encoding genes were isolated from a red-necked wallaby (Macropus rufogriseus) cDNA library by using a chimpanzee DRB probe, and their nucleotide sequences were determined. The genes are not orthologous to any of the genes in mammals studied thus far but belong to two new families which we designated Maru-DAB and Maru-DBB. One of the three sequences (DAB2) seems to be derived from a transcribed pseudogene; it lacks the codons specifying the first 51 amino acid residues of the beta 2 domain. The fact that the DAB and DBB families have thus far not been found in placental mammals and that none of the DOB, DPB, DQB, or DRB genes seems to be expressed in the one representative marsupial species can be interpreted as suggesting that class II gene families of eutherian and metatherian mammals evolved from different ancestral genes.

Amino Acid Sequence↗
PubMed1991

[Primary antiphospholipid syndrome: clinical experience of 6 patients].

Recently, the association between anti-phospholipid antibodies (false positive VDRL, lupus anticoagulant or anti-cardiolipin antibody) and diverse clinical manifestations has been termed antiphospholipid syndrome. We report 6 female patients with "primary" antiphospholipid syndrome, not related to connective tissue disorders. Their age ranged from 23 to 66 years and they were followed from 1 to 27 years (mean 9.2). Venous occlusion developed in 4, arterial occlusion in 4 (TIA, convulsive episode and cutaneous thrombotic microangiopathy). Three of 5 had fetal loss and 3/6 developed thrombocytopenia. Leg ulcer, migraine and mitral valvulopathy and peripheral facial paralysis were isolated manifestations in different patients. High titers for type IgG anticardiolipin antibodies were present in all patients. Low titers for IgM antibodies were present in 2. The pathogenesis of this syndrome is discussed.

Adult↗
PubMed1991

[Infections in systemic lupus erythematosus].

In this review of 159 pts with systemic lupus erythematosus (SLE) followed for 18 years, 78 pts had major infections (20/100 pt-years). Patients with infection had a higher incidence of proteinuria, central nervous system involvement, the use of methylprednisolone boluses and mortality rate. Infection was independent of the amount of steroids and immunosuppressor drugs used. Microorganisms were isolated in 77% of the cases, gram negative enterobacteria were the most common isolates. 30% of the pts had pulmonary infection; and 84% of the infections happened during steroid therapy. Immunosuppression was associated to repeated infections. The 19 pts with fatal infections had a higher frequency of pneumonia and septicemia, and received high doses of steroids (> or = 40 mg). No relation to immunosuppression was found in this group. In 26% opportunistic microorganisms were isolated in association to the use of high doses of steroids. Even if survival of SLE has improved in the last 40 years, infections are still an important cause of mortality, most of them related to aggressive steroid therapy.

Adolescent↗
PubMed1990

Organization of the chimpanzee C4-CYP21 region: implications for the evolution of human genes.

We prepared a cosmid library from chimpanzee DNA and screened it with a mouse probe specific for the complement component 4 (C4)-encoding gene. We isolated 29 clones and constructed restriction maps for 20 of these. The clones could be arranged into two overlapping clusters covering the entire C4 region of both chromosomes in this particular heterozygous chimpanzee. The region is about 100 kilobases (kb) long and contains two C4 and two CYP21 genes, the latter coding for the enzyme 21-hydroxylase. Using oligonucleotide probes we identified the genes as corresponding to human C4A, C4B, CYP21 and CYP21P genes. The last gene apparently contains an 8-base pair (bp) deletion (as does the corresponding human gene), which renders it a pseudogene. The genes are arranged in the order C4A...CYP21P...C4B...CYP21. Each of the two C4 genes is 16 kb long and thus corresponds to the short version of the human C4 genes. We suggest that the duplication of the basic C4-CYP21 unit that generated the standard arrangement of the human C4-CYP21 region occurred before the separation of the evolutionary lineages leading to humans and chimpanzees (i.e., more than five million years ago). We suggest further that the original form of the C4 gene was of the long variety and was generated by the insertion of a 6.8-kb element into one of the C4 introns. The element was subsequently excised in the ancestors of the chimpanzees and in at least one lineage of the human C4B gene. We speculate that the presence of the 6.8-kb insert in the human C4A and some C4B genes might largely be responsible for the great instability of this chromosomal region which leads to frequent duplications and deletions, some of which cause 21-hydroxylase deficiency.

Animals↗