- FRC Blood Service, Helsinki, Finland
Jukka Partanen
University of Helsinki, Genetics, Adjunct
The gene CYP21B, encoding the steroid 21-hydroxylase enzyme of adrenal steroid biosynthesis, has been mapped to the human major histocompatibility complex (MHC). Deficiency of this enzyme leads to congenital adrenal hyperplasia (CAH). We... more
The gene CYP21B, encoding the steroid 21-hydroxylase enzyme of adrenal steroid biosynthesis, has been mapped to the human major histocompatibility complex (MHC). Deficiency of this enzyme leads to congenital adrenal hyperplasia (CAH). We report the phenotypes of the HLA and complement C4 and Bf genes, which are closely linked to the CYP21B gene, together with a detailed analysis of the CYP21 and C4 RFLP, in 17 Finnish families with CAH. The RFLP analysis with six restriction enzymes suggested that, altogether, 35% of the affected chromosomes had a CYP21B + C4B gene deletion, 9% an obvious gene conversion of the CYP21B gene to a CYP21A-like gene, and 3% a CYP21A + C4B duplication. The remaining 53% gave the RFLP patterns also found in nonaffected chromosomes. We also found that a 14.0-kb EcoRI RFLP marker of the CYP21 genes was strongly associated with the presence of a short C4B gene, suggesting that some of the RFLP markers found with the CYP21 probe may actually derive from C4B ge...
Research Interests: Genetics, Biology, Medicine, Biological Sciences, Population, and 12 moreHumans, Gene, Gene Duplication, Phenotype, Genetic linkage analysis, Congenital Adrenal Hyperplasia, Major histocompatibility complex, Genetic Markers, Haplotype, Gene frequency, Chromosome deletion, and Medical and Health Sciences
Research Interests: Genetics, Immunology, Biology, Cell Biology, Medicine, and 15 moreCell line, Humans, Autoimmune diseases, Celiac Disease, Haplotypes, Phenotype, Clinical Sciences, Gene Polymorphism, Major histocompatibility complex, Linkage Disequilibrium, Heat Shock Proteins, Heat Shock Protein, Allele, Allele Frequency, and Haplotype
ABSTRACT
Research Interests:
In coeliac disease, autoantibodies directed against transglutaminase 2 are produced in small-bowel mucosa, and they have been found to be deposited extracellularly. The aim of this study was to investigate whether such mucosal IgA... more
In coeliac disease, autoantibodies directed against transglutaminase 2 are produced in small-bowel mucosa, and they have been found to be deposited extracellularly. The aim of this study was to investigate whether such mucosal IgA deposits are important in the diagnostic work-up of early-stage coeliac disease without small-bowel mucosal villous atrophy. Forty-one adults suspected of coeliac disease owing to increased density of mucosal gamma(delta)+ intraepithelial lymphocytes but normal villous morphology were randomized to gluten challenge or a gluten-free diet for 6 months. Clinically and histologically verified gluten dependency was compared with existence of small-bowel mucosal transglutaminase 2-specific extracellular IgA deposits and (coeliac disease-type) HLA DQ2 and DQ8; 34 non-coeliac subjects and 18 patients with classical coeliac disease served as controls. Of the 41 patients, 5 in the challenge group and 6 in the gluten-free diet group were clinically gluten sensitive; all 11 had HLA DQ2 or DQ8. Ten of these 11 patients showed transglutaminase 2-targeted mucosal IgA deposits, which were dependent on gluten consumption. Minimal IgA deposits were seen in only 3 out of 30 patients with suspected coeliac disease without any clinically detected gluten dependency. The deposits were found in all classical coeliac patients and in none of the non-coeliac control subjects. Clinically pertinent coeliac disease exists despite normal small-bowel mucosal villous architecture. Mucosal transglutaminase 2-specific IgA deposits can be utilized in detecting such patients with genetic gluten intolerance.
Research Interests:
Research Interests:
Research Interests: Genetics, Human Genetics, Immunology, Molecular Biology, Polymorphism, and 15 moreBiology, Medicine, Immunogenetics, Humans, von Willebrand factor, P-glycoprotein, Gene, Genetic Polymorphism, Amino Acid Sequence, Base Sequence, Allele, Cell Surface Markers, Molecular Sequence Data, alleles, and Blood Donor
We study a set of samples with non-deleted C4Q0 genes but by using, firstly, Taq I with the full-length cDNA probes pAT-A for C4 genes and p21/c2 for CYP21 genes to characterise the overall organisation of the C4 genes (loci A and B), and... more
We study a set of samples with non-deleted C4Q0 genes but by using, firstly, Taq I with the full-length cDNA probes pAT-A for C4 genes and p21/c2 for CYP21 genes to characterise the overall organisation of the C4 genes (loci A and B), and secondly, Nla IV and Eco 0109 digestions to analyse the critical C4d region in more detail (C4A/C4B isotypes and Rg1/Ch1 determinants)
Research Interests: Genetics, Immunology, Biology, Medicine, Immunogenetics, and 7 moreHumans, Mutation, Haplotypes, Gene, Gene Conversion, Allele, and alleles
Research Interests:
... Oscar G. Segurado xy, Paz Iglesias-Casarrubios l, Pablo Morales 1, Jorge Martinez-Laso 1, Jukka Partanen 2, R. Duncan Campbell 3, and ... Tissue Antigens 20: 123-140, 1982 Dunham, I., Sargent, CA, Trowsdale, J., and Campbell, RD:... more
... Oscar G. Segurado xy, Paz Iglesias-Casarrubios l, Pablo Morales 1, Jorge Martinez-Laso 1, Jukka Partanen 2, R. Duncan Campbell 3, and ... Tissue Antigens 20: 123-140, 1982 Dunham, I., Sargent, CA, Trowsdale, J., and Campbell, RD: Molecular mapping of the human major ...
Research Interests:
Research Interests:
Research Interests:
Research Interests: Genetics, Immunology, Biology, Medicine, Finland, and 15 moreCell line, Humans, Haplotypes, Polymerase Chain Reaction, Gene Polymorphism, Major histocompatibility complex, Human Immunology, Base Sequence, Allele, Genetic Markers, General Population, Haplotype, Founder Effect, Molecular Sequence Data, and Human leukocyte antigen
Research Interests:
Infertility is assumed to arise exclusively from male- and female-dependent pathological factors. However, recent studies have indicated that reproductive failure may also result from the reproductive incompatibility of the partners.... more
Infertility is assumed to arise exclusively from male- and female-dependent pathological factors. However, recent studies have indicated that reproductive failure may also result from the reproductive incompatibility of the partners. Selection against such incompatibilities likely occurs via female-derived reproductive secretions, including follicular fluid (FF), that mediate gamete-level mate choice towards the sperm of specific males. To facilitate potential development of diagnostic tests for human reproductive incompatibility, we examined whether sperm physiological response to female serum indicate male–female compatibility in the presence of FF. We performed a full-factorial experiment, in which the sperm of 10 males were treated with the FF and serum of 6 healthy females. We found that sperm motility and viability in both biofluids were highly similar and that in 70% of the males, sperm serum treatment predicted male–female compatibility. We also identified male human leucocy...
Research Interests: Genetics, Biology, Infertility, Medicine, Sperm, and 6 moreMale Infertility, Molecular sciences, Gamete, Semen, Sperm Motility, and Allele
Research Interests:
Research Interests:
Background: There is increasing evidence that frequent blood donation depletes the iron stores of some but not all blood donors. To identify risk groups and factors affecting the iron stores in the Finnish donor population the Fin Donor... more
Background: There is increasing evidence that frequent blood donation depletes the iron stores of some but not all blood donors. To identify risk groups and factors affecting the iron stores in the Finnish donor population the Fin Donor 10 000 project, a prospective study observing blood donor iron stores and genetic and lifestyle factors associated with iron stores, was set up. Material and methods: 2584 blood donors (N= 8003 samples) were recruited in the study alongside the standard donation at three fixed donation sites in the capital region of Finland during 5/2015 - 12/2017. All participants were asked to fill in a pseudonymized questionnaire about their health and lifestyle; 2562 donors (99.1%) completed it. Blood samples were collected from the sample pouch of whole blood collection set, kept in cool temperature and processed centrally. The samples were sent to a clinical laboratory for analysis of whole blood count, CRP, ferritin and sTFR; in addition, genomic DNA was isola...
Research Interests:
The human leukocyte antigen (HLA) genes code for proteins that play a central role in the function of the immune system by presenting peptide antigens to T cells. As HLA genes show extremely high genetic polymorphism, HLA typing at the... more
The human leukocyte antigen (HLA) genes code for proteins that play a central role in the function of the immune system by presenting peptide antigens to T cells. As HLA genes show extremely high genetic polymorphism, HLA typing at the allele level is demanding and is based on DNA sequencing. Determination of HLA alleles is warranted as HLA alleles are major genetic risk factors in autoimmune diseases and are matched in transplantation. Here, we compared the accuracy of several published HLA-typing algorithms that are based on next-generation sequencing (NGS) data. As genome sequencing is becoming increasingly common in research, we wanted to test how well HLA alleles can be deduced from genome data produced in studies with objectives other than HLA typing and in platforms not especially designed for HLA typing. The accuracies were assessed using datasets consisting of NGS data produced using an in-house sequencing platform, including the full 4 Mbp HLA segment, from 94 stem cell tr...
Research Interests:
Key Points We used a registry containing all 1 163 524 blood donor returns that took place in Finland between 2010 and 2015 to evaluate cHb recovery. Average recovery times for cHb to return to the level of the preceding donation were... more
Key Points We used a registry containing all 1 163 524 blood donor returns that took place in Finland between 2010 and 2015 to evaluate cHb recovery. Average recovery times for cHb to return to the level of the preceding donation were longer than the minimum allowed donation intervals.
Research Interests:
The human leukocyte antigen (HLA) genes code for proteins that play a central role in the function of the immune system by presenting peptide antigens to T cells. As HLA genes show extremely high genetic polymorphism, HLA typing on the... more
The human leukocyte antigen (HLA) genes code for proteins that play a central role in the function of the immune system by presenting peptide antigens to T cells. As HLA genes show extremely high genetic polymorphism, HLA typing on the allele level is demanding and is based on DNA sequencing. Determination of HLA alleles is warranted as many HLA alleles are major genetic factors that confer susceptibility to autoimmune diseases and is important for the matching of HLA alleles in transplantation. Here, we compared the accuracy of several published HLA-typing algorithms that are based on next generation sequencing (NGS) data. As genome screens are becoming increasingly routine in research, we wanted to test how well HLA alleles can be deduced from genome screens not designed for HLA typing. The accuracies were assessed using datasets consisting of NGS data produced using the ImmunoSEQ platform, including the full 4 Mbp HLA segment, from 94 stem cell transplantation patients and exome ...
Research Interests:
Research Interests:
Research Interests: Polymorphism, Kidney transplantation, Cytokines, Medicine, Renal transplantation, and 15 moreHumans, Internal Medicine, Female, Male, Clinical Sciences, Cadaver, Middle Aged, Gene Polymorphism, Kidney Transplant, Graft Rejection, Acute rejection, Postoperative Complications, Acute Disease, Infarction, and High risk
Research Interests:
Research Interests:
Background Allogeneic therapeutic cells may be rejected if they express HLA alleles not found in the recipient. As finding cell donors with a full HLA match to a recipient requires vast donor pools, the use of HLA homozygous cells has... more
Background Allogeneic therapeutic cells may be rejected if they express HLA alleles not found in the recipient. As finding cell donors with a full HLA match to a recipient requires vast donor pools, the use of HLA homozygous cells has been suggested as an alternative. HLA homozygous cells should be well tolerated by those who carry at least one copy of donor HLA alleles. HLA-A-B homozygotes could be valuable for HLA-matched thrombocyte products. We evaluated the feasibility of blood donor biobank and HLA imputation for the identification of potential cell donors homozygous for HLA alleles. Methods We imputed HLA-A, -B, -C, -DRB1, -DQA1, -DQB1 and -DPB1 alleles from genotypes of 20,737 Finnish blood donors in the Blood Service Biobank. We confirmed homozygosity by sequencing HLA alleles in 30 samples and by examining 36,161 MHC-located polymorphic DNA markers. Results Three hundred and seventeen individuals (1.5%), representing 41 different haplotypes, were found to be homozygous for...
Research Interests:
The human leukocyte antigen (HLA) system is the single most important genetic susceptibility factor for many autoimmune diseases and immunological traits. However, in a range of clinical phenotypes the impact of HLA alleles or their... more
The human leukocyte antigen (HLA) system is the single most important genetic susceptibility factor for many autoimmune diseases and immunological traits. However, in a range of clinical phenotypes the impact of HLA alleles or their combinations on the disease risk are not comprehensively understood.For systematic population-level analysis of HLA-phenotype associations we imputed the alleles of classical HLA genes in a discovery cohort of 146,630 and replication cohort of 89,340 Finns of whom SNP genotype data and 3,355 disease phenotypes were available as part of the FinnGen project.The results suggest HLA associations in phenotypes not reported previously and highlight interactions between HLA genes and alleles in autoimmune diseases. Furthermore, shared HLA alleles in autoimmune and infectious diseases support a genetic link between these diseases.
Research Interests:
Matching classical HLA alleles between donor and recipient is an important factor in avoiding adverse immunological effects in HSCT. Siblings with no differences in HLA alleles, either due to identical-by-state or identical-by-descent... more
Matching classical HLA alleles between donor and recipient is an important factor in avoiding adverse immunological effects in HSCT. Siblings with no differences in HLA alleles, either due to identical-by-state or identical-by-descent status, are considered to be optimal donors. We carried out a retrospective genomic sequence and SNP analysis of 336 fully HLA-A, -B, -DRB1 matched and 14 partially HLA-matched sibling HSCT pairs to determine the level of undetected mismatching within the MHC segment as well as to map their recombination sites. The genomic sequence of 34 genes locating in the MHC region revealed allelic mismatching at 1 to 8 additional genes in partially HLA-matched pairs. Also, fully matched pairs were found to have mismatching either at HLA-DPB1 or at non-HLA region within the MHC segment. Altogether, 3.9% of fully HLA-matched HSCT pairs had large genomic mismatching in the MHC segment. Recombination sites mapped to certain restricted locations. The number of mismatc...
Research Interests:
Increasing numbers of blood donors are recruited to participate in biomedical research. As blood services depend on voluntary donors, successful recruitment calls for a better understanding of donors' expectations and attitudes toward... more
Increasing numbers of blood donors are recruited to participate in biomedical research. As blood services depend on voluntary donors, successful recruitment calls for a better understanding of donors' expectations and attitudes toward the use of samples in research. Sixty-one semistructured interviews were conducted with blood donors at eight Finnish Red Cross Blood Service donation sites in Finland. The 10- to 30-minute interviews included open-ended questions about donors' views on blood donation for patients and for biomedical research. Central motives to donate blood for patients were identified against which views on research use were compared to see how these reflections differed. Six central motives for donating blood for patients were identified among donors. The interviewees were, in general, willing to donate blood for research, but considered research donation more likely if it could be easily integrated into their usual blood donation habits. Biomedical research ...
Research Interests:
From 11 studies, a total of 1,792 Caucasian probands with insulin-dependent diabetes mellitus (IDDM) are analyzed. Antigen genotype frequencies in patients, transmission from affected parents to affected children, and the relative... more
From 11 studies, a total of 1,792 Caucasian probands with insulin-dependent diabetes mellitus (IDDM) are analyzed. Antigen genotype frequencies in patients, transmission from affected parents to affected children, and the relative frequencies of HLA-DR3 and -DR4 homozygous patients all indicate that DR3 predisposes in a "recessive"-like and DR4 in a "dominant"-like or "intermediate" fashion, after allowing for the DR3/DR4 synergistic effect. Removal of DR3 and DR4 reveals an overall protective effect of DR2, predisposing effects of DR1 and DRw8, and a slight protective effect of DR5 and a predisposing effect of DRw6. Analysis of affected-parent-to-affected-child data indicates that a subset of DR2 may predispose. The non-DR3, non-DR4 antigens are not independently associated with DR3 and DR4; the largest effect is a deficiency of DR2, followed by excesses of DR1, DRw8, and DRw6, in DR4 individuals, as compared with DR3 individuals. HLA-B locus distribut...
Research Interests: Biology, Adolescent, Medicine, Disease susceptibility, Biological Sciences, and 15 moreHumans, Child, Diabetes mellitus, Haplotypes, Female, Male, Infant, American, Age Factors, European Continental Ancestry Group, Genetic variation, Elsevier, Child preschool, Gene frequency, and Medical and Health Sciences
Research Interests:
Research Interests: Adolescent, Medicine, Humans, Child, Intestinal Mucosa, and 15 moreCeliac Disease, Female, Male, Infant, Clinical Sciences, Middle Aged, Atrophy, Adult, Major histocompatibility complex, Sensitivity and Specificity, Gluten Free Diet, The American, Child preschool, small bowel, and Human leukocyte antigen
Research Interests:
Research Interests:
Killer cell immunoglobulin-like receptors (KIRs) belong to a diverse family of natural killer (NK) cell receptors recognizing human leukocyte antigen (HLA) class I molecules. Due to this functional link, KIR molecules are expected to... more
Killer cell immunoglobulin-like receptors (KIRs) belong to a diverse family of natural killer (NK) cell receptors recognizing human leukocyte antigen (HLA) class I molecules. Due to this functional link, KIR molecules are expected to display a high polymorphism, such as their HLA ligands. Moreover, many studies conducted in mouse and human models have shown that NK-KIR receptors play an important role in haematopoietic stem cell transplantation (HSCT). A beneficial impact of peculiar KIR ligand (HLA) mismatching has been reported suggesting a role to this combinatory HLA-KIR polymorphism. It is thus important to investigate KIR diversity in various human populations. To this end, we used polymerase chain reaction-sequence-specific primers to evaluate KIR gene in five selected populations (France, Guadeloupe, Senegal, Finland and Réunion). Genotypic and haplotypic frequencies were computed, as well as genetic distances and dendrogram (phylip package). These data illustrate the genetic relationship of these five populations through the KIR polymorphism. Results revealed a wide diversity in KIR gene frequencies in Guadeloupe and Réunion, and a high specificity in Senegal. The obtained dendrogram indicated small genetic distances between France, Guadeloupe and Réunion as well as between France and Finland. Senegal showed a distant genetic relationship with the other countries and, interestingly, an inverted ratio of coding/non-coding (KIR2DS4/1D) alleles compared with Caucasians. These data expose the broad diversity in KIR genes worldwide and show that KIR genes are pertinent tools in human population genetics. If the role of KIR donor-recipient incompatibilities is confirmed, KIR diversity according to ethnicity should be taken into account during the selection of HSCT donors.
Research Interests:
Haplotypes including HLA, Bf and C4 loci were analyzed in a material comprising 55 families with diabetic children. One hundred and ten haplotypes found in IDDM patients were compared with 101 haplotypes present only in healthy family... more
Haplotypes including HLA, Bf and C4 loci were analyzed in a material comprising 55 families with diabetic children. One hundred and ten haplotypes found in IDDM patients were compared with 101 haplotypes present only in healthy family members. Two complotypes, BfSC4A3B3 and SC4A0B1, were significantly more common (P less than 0.05) in the diabetic haplotypes, and these were in most cases found in haplotypic combinations with HLA-B15,Dw4,DR4 and HLA-B8,Dw3,DR3 genes, respectively. The B8/DR3 haplotype was better conserved, as 72% included the BfSC4A0B1 complotype as compared with only 35% of the B15/DR4 haplotypes with "high risk" C4A3B3 complement alleles (p less than 0.05). DR3 was found in 26% of the diabetic haplotypes and DR4 in 43%. DR4 associated with the Dw4 in 69% of cases and with Dw14 in 26% of the diabetic haplotypes. Our results confirm that the two phenotypes found earlier to be associated with IDDM in Northern Finland, e.g. "B15,BfS,C4A3B3,Dw4,DR4" and "B8,Bfs,C4A0B1,Dw3,DR3" are inherited as haplotypes.
Research Interests:
One hundred and thirty-six Finnish patients with insulin-dependent (type I) diabetes mellitus were investigated for the HLA-A, B, D and DR antigens as well as the Bf and C4 allotypes. The statistically significant increase in the... more
One hundred and thirty-six Finnish patients with insulin-dependent (type I) diabetes mellitus were investigated for the HLA-A, B, D and DR antigens as well as the Bf and C4 allotypes. The statistically significant increase in the frequencies of HLA-A9, B8, B15, Dw3, Dw4, DR3, DR4, C4A0 and C4B3 was observed when compared with the healthy controls. About 79% of the patients had HLA-DR4, and 53% had HLA-DR3 antigens. A rare C4 allele C4B3 was found in 21% of the patients, whereas only in 2% among the controls (relative risk 16.35). The etiological fraction (EF) values indicated that HLA D/DR alleles were the best markers for IDDM, the observed EF for HLA-DR4 in diabetes was as high as 0.70. Examination of HLA, Bf and C4 phenotypes suggested that at least two supratypes "B15 BfS C4A3B3 D(R)4" and "B8 BfS C4A0B1 D(R)3" were markers for the susceptibility to type I diabetes, one third of our patients had either of these supratypes. The protective role of DR2 and Dw2 antigens was also confirmed: no HLA-Dw2 positive patients and only one with HLA-DR2 was found.
Research Interests:
Research Interests: Technology, Biology, Induced Pluripotent Stem Cells (I Psc), Cell Biology, Medicine, and 11 moreBiological Sciences, Cell line, Cell Differentiation, Humans, Embryonic Stem Cells, Plant Lectins, Hepatocytes, Cell Proliferation, Induced Pluripotent Stem Cells, Pluripotent Stem Cells, and Medical and Health Sciences
Research Interests: Adolescent, Medicine, Humans, Celiac Disease, Gliadin, and 15 moreFemale, Male, Clinical Sciences, Prevalence, Middle Aged, Adult, Esophagus, Blood Donors, Enzyme Linked Immunosorbent Assay, Autoantibodies, immunoglobulin G, Random Allocation, Immunoglobulin A, Blood Donor, and Muscle fibers skeletal
We analyzed the HLA class II haplotypes in 249 Finnish nuclear families and compared the frequencies of parental haplotypes transmitted or non-transmitted to multiple sclerosis (MS) patients. The most important predisposing haplotype was... more
We analyzed the HLA class II haplotypes in 249 Finnish nuclear families and compared the frequencies of parental haplotypes transmitted or non-transmitted to multiple sclerosis (MS) patients. The most important predisposing haplotype was DRB1*15-DQB1*0602 (P<10(-6)) as expected and a weak predisposing effect of DRB1*04-DQB1*0302 was revealed after the elimination of DRB1*15-DQB1*0602. HLA-DRB1*01-DQB1*0501 and DRB1*13-DQB1*0603 were negatively associated with MS in transmission disequilibrium test, but only the DRB1*13-DQB1*0603 association remained significant (P=0.008) after the elimination of DRB1*15-DQB1*0602 haplotypes. Based on this study HLA class II haplotypes exhibit both predisposing and protective effects in MS.