Mats Sundvall - Academia.edu (original) (raw)

Papers by Mats Sundvall

Molecular Evolution of the Major Histocompatibility Complex, 1991

Journal of immunology (Baltimore, Md. : 1950), 1999

The susceptibility to collagen-induced arthritis in the highly susceptible DBA/1 mouse has earlie... more The susceptibility to collagen-induced arthritis in the highly susceptible DBA/1 mouse has earlier been shown to be partly controlled by the MHC class II gene Aq. To identify susceptibility loci outside of MHC, we have made crosses between DBA/1 and the less susceptible B10.Q strain, both expressing the MHC class II gene Aq. Analysis of 224 F2 intercross mice with 170 microsatellite markers in a genome-wide scan suggested 4 quantitative trait loci controlling arthritis susceptibility located on chromosomes 6, 7, 8, and 10. The locus on chromosome 6 (Cia6), which was associated with arthritis onset, yielded a logarithm of odds score of 4.7 in the F2 intercross experiment and was reproduced in serial backcross experiments. Surprisingly, the DBA/1 allele had a recessive effect leading to a delay in arthritis onset. The suggestive loci on chromosomes 7 and 10 were associated with arthritis severity rather than onset, and another suggestive locus on chromosome 8 was most closely associat...

Nature genetics, 1998

Rheumatoid arthritis (RA) is a chronic and genetically complex inflammatory disorder that leads t... more Rheumatoid arthritis (RA) is a chronic and genetically complex inflammatory disorder that leads to erosive destruction of peripheral joints. The use of animal models mimicking RA, such as pristane-induced arthritis (PIA) in rats, should facilitate its genetic analysis. Pristane is a non-immunogenic synthetic oil that, after a single subcutaneous injection into DA rats, induces arthritis restricted to peripheral joints with a chronic relapsing disease course. To identify genes involved in the control of chronic arthritis, we made crosses between susceptible DA rats and resistant E3 rats and analysed the progeny with microsatellite markers covering the entire rat genome. Our results show that different arthritis phenotypes are associated with different chromosomal loci. Loci on chromosomes 4 and 6 (Pia2 and Pia3) influence arthritis onset, whereas a locus on chromosome 12 (Pia4) is associated with severity and joint erosion. We found that chronicity is associated with a different set ...

American journal of human genetics, 1993

A four-generation Swedish family with a new type of X-linked mental retardation syndrome was rece... more A four-generation Swedish family with a new type of X-linked mental retardation syndrome was recently reported by Gustavson et al. The complex syndrome includes microcephaly, severe mental retardation, optical atrophy with decreased vision or blindness, severe hearing defect, characteristic facial features, spasticity, seizures, and restricted joint motility. The patients die during infancy or early in childhood. Twenty-one family members, including two affected males, were available for study. Linkage analysis was conducted in the family by using 11 RFLP markers and 10 VNTR markers spread along the X chromosome. A hypervariable short tandem repeat of DXS294 at Xq26 showed a peak two-point lod score of 3.35 at zero recombination fraction. Calculations using the same markers revealed a multipoint peak lod score of 3.65 at DXS294. Crossover events with the centromeric marker DXS424 and the telomeric marker DXS297 delimit a probable region for the gene localization. It is noteworthy th...

Tissue Antigens, 1996

consistent with symmetric balancing selection, the distribution of DPBl alleles in human populati... more consistent with symmetric balancing selection, the distribution of DPBl alleles in human populations is more J-shaped. A single predominant allele is usually found in each population, although the identity of the most frequent allele differs among various human populations (5, 7). The homozygosity statistic (F) indicates that the allele frequency distribution for DPBl does not deviate from that expected under conditions of neutrality, in cqntrast to the pattern found for other polymorphic class I1 genes (7). These observations suggest a different mechanism of maintenance for the DPBl allelic variation from that for other polymorphic Mhc class 11 loci. To provide an evolutionary framework within which to interpret the polymorphism found in humans we have analyzed the allelic variability at DPBl in two species of chimpanzee and in the gorilla.

Proceedings of the National Academy of Sciences, 1991

The loci encoding the class II cell surface antigens HLA-DR,-DQ, and-DP exhibit a remarkable degr... more The loci encoding the class II cell surface antigens HLA-DR,-DQ, and-DP exhibit a remarkable degree of aflelic polymorphism. Most of the class I allelic diversity is localized to the second exon, which encodes a fl-pleated sheet followed by an a-helical domain. Here, phylogenetic analysis of

Proceedings of the National Academy of Sciences, 1986

A genomic DNA fragment that encodes a Plasmodium falciparum antigen has been isolated by using hu... more A genomic DNA fragment that encodes a Plasmodium falciparum antigen has been isolated by using human antibodies eluted from the membrane of infected erythrocytes. The antigen has a very unusual primary structure; it is exceptionally rich in asparagine residues, many of which are distributed in dusters (2-15 residues) along the polypeptide chain. Unlike many P. falciparum antigens, this protein lacks tandemly repeated sequences. The antigen is distinct from Pf 155, a merozoite-derived antigen deposited in the membrane of infected erythrocytes, but contains epitopes that crossreact with anti-Pf 155 antibodies. Antisera prepared in mice against the asparagine-rich protein react with late-stage parasites in indirect immunofluorescence. In an in vitro merozoite reinvasion assay, the IgG fraction of a mouse polyclonal antiserum, as well as a mouse monoclonal antibody, gave significant inhibition. Three polypeptides (Mr 36,000, 30,000, and 15,000) were recognized by these antibodies on immunoblots of P. falciparun extracts.

Nucleic Acids Research, 1992

Nature Genetics, 1995

B10.RIII mice develop chronic and relapsing experimental autoimmune encephalomyelitis (EAE) after... more B10.RIII mice develop chronic and relapsing experimental autoimmune encephalomyelitis (EAE) after immunization with the myelin basic protein (MBP) peptide 89-101. The disease is associated with the major histocompatibility complex (MHC) (eae1). We have now investigated the importance of non-MHC regions for the EAE susceptibility in a cross between RIIIS/J and B10.RIII mice which share the MHC region but differ in disease susceptibility. Linkage analysis using microsatellite markers spanning the genome identified a region (eae2) on chromosome 15 which showed linkage to disease (P = 0.0002). Our data also suggest linkage to a second region (eae3) on chromosome 3 (P = 0.0024), and provide evidence for locus interactions between eae2 and eae3. These results provide clues to the genetic basis of multiple sclerosis.

Molecular Psychiatry, 1998

Recurrent major depression, RMD, is characterized by the occurrence of depressive episodes in the... more Recurrent major depression, RMD, is characterized by the occurrence of depressive episodes in the absence of mania and/or hypomania. In linkage studies, RMD (or, in general, unipolar depression) are frequently grouped together with bipolar illnesses into a broad definition of affective disorders. However, twin studies suggest that RMD and bipolar disorders might have different genetic determinants. The objective of this study was to test a set of families with RMD for linkage to chromosomes that have been recently proposed to contain susceptibility loci for bipolar disorders: chromosomes 16, 18, 21 and the short arm of chromosome 4. We analysed five large families from the northern part of Sweden ascertained through a proband with RMD and containing several patients with RMD. For the genetic analysis, we included only severely affected individuals (those who had at least three episodes that required medical treatment) to increase the chances of finding a larger degree of genetic determination. The genetic model led to a total disease prevalence of 5% in females and 3% in males. We did not find significant evidence for linkage to any of the candidate chromosomes in the combined family set. Only one of the families showed a slight indication for linkage with markers from the pericentromeric region of chromosome 18. A genome scan analysis on an extended collaborative family material with severely affected individuals with RMD should be performed to evaluate whether RMD and bipolar disorders have a different genetic etiology.

Journal of Medical Genetics, 1997

Primary nocturnal enuresis (PNE), or bedwetting at night, affects approximately 10% of 6 year old... more Primary nocturnal enuresis (PNE), or bedwetting at night, affects approximately 10% of 6 year old children. Genetic components contribute to the pathogenesis and recently one locus was assigned to chromosome 13q. We evaluated the genetic factors and the pattern of inheritance for PNE in 392 families. Dominant transmission was observed in 43% and an apparent recessive mode of inheritance was observed in 9% ofthe families. Among the 392 probands the ratio of males to females was 3:1 indicating sex linked or sex influenced factors. Linkage to candidate regions was tested in 16 larger families segregating for autosomal dominant PNE. A gene for PNE was excluded from chromosome 13q in 11 families, whereas linkage to the interval D13S263-D13S291 was suggested (Zmax=2.1) in three families. Further linkage analyses excluded about 1/3 of the genome at a 10 cM resolution except the region around D12S80 on chromosome 12q that showed a positive two point lod score in six of the families (Zmax=4.2). This locus remains suggestive because the material was not sufficiently large to give evidence for heterogeneity. Our pedigree analysis indicates that major genes are involved in a large proportion of PNE families and the linkage results suggest that such a gene is located on chromosome 12q.

Journal of Experimental Animal Science, 2000

... Experimental Animal Science Genetic control of arthritis in rats RIKARD HOLMDAHL 1, CARINA VI... more ... Experimental Animal Science Genetic control of arthritis in rats RIKARD HOLMDAHL 1, CARINA VINGSBO-LUNDBERG 1, NIKLAS NORDQUIST 2, PETER OLOFSSON l, MATS SUNDVALL 2 ... 12. HOLMDAHL, R., C. NORDLING, K. RUBIN, A. TARKOWSKI, and L. KLARESKOG. ...

Immunogenetics, 1994

Cotton-top tamarins (Saguinus oedipus) in captivity are unusual in that they exhibit low levels o... more Cotton-top tamarins (Saguinus oedipus) in captivity are unusual in that they exhibit low levels of polymorphism and allelic diversity at the major histocompatibility complex (Mhc) class I loci. Since the polymorphism has previously only been examined in captive tamarins, we analyzed the Mhc class I alleles of a population of wild tamarins. These wild tamarins, like their captive counterparts, exhibited limited class I polymorphism. We also assessed the levels of polymorphism and allelic diversity at the Mhc class II DQA1, DQB1, DQB2, and the DRB loci in captive populations of cotton-top tamarins. In contrast to the extensive polymorphism in Old World monkeys, only two alleles were detected at each of DQA1 and DQB1. Also, the DQB2 locus was monomorphic and conserved between New and Old World monkeys. Sequences derived from four putative DRB loci were obtained, and extensive polymorphism was found at all four loci. Phylogenetic The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession numbers L32096-L32122 u. Gyllensten (~) • T. Bergstr6m • A

Gene, 1988

The nucleotide sequences of the introns that are located between the C4 exon and the first membra... more The nucleotide sequences of the introns that are located between the C4 exon and the first membrane exon of mouse and rat immunoglobulin epsilon-chain genes have been determined. The rat intron sequence was found to contain four separate clusters of repetitive sequences all of which consisted of (dC-dA)n.(dG-dT)n dinucleotide repeats. A comparison between this chromosomal region in mouse and rat revealed four deletions or duplications, three of which have occurred inside or at the borders of the CA clusters. Rearrangements have occurred inside or at the borders of all four repeats after the evolutionary separation of mouse and rat. The sequence comparison reveals in addition a duplication, connected to the CA repeats, which has occurred early in evolution, before the evolutionary divergence of mouse and rat. These findings suggest that (dC-dA)n.(dG-dT)n sequences are potential targets for recombination events.

European Journal of Immunology, 1998

The genetic susceptibility to collagen-induced arthritis (CIA) in mice, the most commonly used mo... more The genetic susceptibility to collagen-induced arthritis (CIA) in mice, the most commonly used model for rheumatoid arthritis, has been analyzed. The highly susceptible B10.RIII strain was crossed with the resistant RIIIS/J strain and the F2 intercross mice were subjected to genomic screening using microsatellite markers. These strains share the MHC region on chromosome 17, known to be of importance in CIA (this locus is named Mcia1). The same cross has earlier been used to map the major genes outside the MHC controlling chronic relapsing experimental allergic encephalomyelitis (EAE). It was found that the major locus controlling CIA (Mcia2; lod 4.12) was located on chromosome 3 in the same region as one of the major loci controlling EAE (Eae3). The linkage was reproduced in a mouse strain in which the locus was isolated on the B10.RIII background at the N4I2 generation. A second putative locus was identified on chromosome 13 (lod 3.13). The present finding identifies new loci outside the MHC controlling CIA and provides evidence that mouse CIA is controlled by polymorphic genes.

Clinical Genetics, 2008

Linkage analysis was performed in three Swedish families segregating for X-linked retinitis pigme... more Linkage analysis was performed in three Swedish families segregating for X-linked retinitis pigmentosa (XLRP). using five polymorphic DNA markers assigned to Xp. Individual recombination events were analyzed and two-and five-point linkage analysis was undertaken. In one family, a XLRP locus was mapped to the same position as OTC corresponding to RP3. In two families, a disease locus linked to OTC was excluded. In one family, recombination events indicate a locus for XLRP outside the interval (DXSS4-0TC-DXS255-DXS14). most likely on the centromeric side of DXS14.