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2. Diagnostic yield of genetic testing in a heterogeneous cohort of 1376 HCM patients

Author

Hathaway, Julie, Heliö, Krista, Saarinen, Inka, Tallila, Jonna, Seppälä, Eija H., Tuupanen, Sari, Turpeinen, Hannu, Kangas-Kontio, Tiia, Schleit, Jennifer, Tommiska, Johanna, Kytölä, Ville, Valori, Miko, Muona, Mikko, Sistonen, Johanna, Gentile, Massimiliano, Salmenperä, Pertteli, Myllykangas, Samuel, Paananen, Jussi, Alastalo, Tero-Pekka, Heliö, Tiina, and Koskenvuo, Juha

Published
2021
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4. Multicenter Analyses Demonstrate Significant Clinical Effects of Minor Histocompatibility Antigens on GvHD and GvL after HLA-Matched Related and Unrelated Hematopoietic Stem Cell Transplantation

Author

Spierings, Eric, Kim, Yeung-Hyen, Hendriks, Matthijs, Borst, Eric, Sergeant, Ruhena, Canossi, Angelica, Oudshoorn, Machteld, Loiseau, Pascale, Dolstra, Harry, Markiewicz, Miroslaw, Leffell, Mary S., Pereira, Noemi, Kircher, Brigitte, Turpeinen, Hannu, Eliaou, Jean-François, Gervais, Thibaut, Laurin, David, Enczmann, Jürgen, Martinetti, Miryam, Thomson, Jackie, Oguz, Fatma, Santarone, Stella, Partanen, Jukka, Siekiera, Urszula, Alessandrino, Emilio Paolo, Kalayoglu, Sevgi, Brand, Ronald, and Goulmy, Els

Published
2013
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6. A genome-wide expression quantitative trait loci analysis of proprotein convertase subtilisin/kexin enzymes identifies a novel regulatory gene variant for FURIN expression and blood pressure

Author

Turpeinen, Hannu, Seppälä, Ilkka, Lyytikäinen, Leo-Pekka, Raitoharju, Emma, Hutri-Kähönen, Nina, Levula, Mari, Oksala, Niku, Waldenberger, Melanie, Klopp, Norman, Illig, Thomas, Mononen, Nina, Laaksonen, Reijo, Raitakari, Olli, Kähönen, Mika, Lehtimäki, Terho, and Pesu, Marko

Published
2015
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8. Additional file 1 of A reverse vaccinology approach on transmembrane carbonic anhydrases from Plasmodium species as vaccine candidates for malaria prevention

Author

Zolfaghari Emameh, Reza, Barker, Harlan R., Turpeinen, Hannu, Parkkila, Seppo, and Hytönen, Vesa P.

Abstract

Additional file 1: Figure S1. W7JAI7 is the representative of group 1 of α-CAs. Figure S2. Q8IHW5 is the representative of group 2 of α-CAs. Figure S3. V7PFH4 is the representative of η-CAs. Figure S4. Multiple sequence analysis (MSA) of W7JAI7 selected from group 1 of transmembrane α-CAs of Plasmodium spp. with human transmembrane α-CAs. Figure S5. Multiple sequence analysis (MSA) of Q8IHW5 selected from group 2 of transmembrane α-CAs of Plasmodium spp. with human transmembrane α-CAs. Figure S6. Multiple sequence analysis (MSA) containing transmembrane η-CA (V7PFH4) of Plasmodium spp. and human transmembrane α-CAs. Figure S7. Prediction of transmembrane localization of representative α- and η-CAs from Plasmodium spp. The prediction identified transmembrane segments near the C-terminal ends of W7JAI7 from group 1 (A) and Q8IHW5 from group 2 (B) of P. falciparum α-CAs and V7PFH4 from P. yoelii η-CAs (C). Figure S8. Pairwise sequence alignment of PDB 2W2J and W7JAI7 V7PFH4 indicating the locations of predicted MHC-I ligands. Figure S9. Pairwise sequence alignment of PDB 3FE4 and Q8IHW5 indicating the locations of predicted MHC-I ligands. Figure S10. Pairwise sequence alignment of PDB 3FE4 and V7PFH4 indicating the locations of predicted MHC-I ligands. Figure S11. Pairwise sequence alignment of PDB 2W2J and W7JAI7 indicating the locations of predicted MHC-II ligands. Figure S12. Pairwise sequence alignment of PDB PDB 3FE4 and Q8IHW5 indicating the location of predicted MHC-II ligand. Figure S13. Pairwise sequence alignment of PDB 3FE4 and V7PFH4 indicating the location of predicted MHC-II ligand.

Published
2022
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13. Identification of proprotein convertase substrates using genome-wide expression correlation analysis

Author

Turpeinen Hannu, Kukkurainen Sampo, Pulkkinen Kati, Kauppila Timo, Ojala Kalle, Hytönen Vesa P, and Pesu Marko

Subjects
Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background Subtilisin/kexin-like proprotein convertase (PCSK) enzymes have important regulatory function in a wide variety of biological processes. PCSKs proteolytically process at a target sequence that contains basic amino acids arginine and lysine, which results in functional maturation of the target protein. In vitro assays have showed significant biochemical redundancy between the seven family members, but the phenotypes of PCSK deficient mice and patients carrying an inactive PCSK allele argue for a specific biological function. Modeling the structures of individual PCSK enzymes has offered little insights into the specificity determinants. However, previous studies have shown that there can be a coordinated expression between a PCSK and its target molecule. Here, we have surveyed the putative PCSK target proteins using genome-wide expression correlation analysis and cleavage site prediction algorithms. Results We first performed a gene expression correlation analysis over the whole genome for all PCSK enzymes. PCSKs were found to cluster differently based on the strength of correlations. The screen for putative PCSK target proteins showed a significant enrichment (p-values from 1.2e-4 to < 1.0e-10) of putative targets among the most positively correlating genes for most PCSKs. Interestingly, there was no enrichment in putative targets among the genes that correlated positively with the biologically redundant PCSK7, whereas PCSK5 showed an inverse correlation. PCSKs also showed a highly variable degree of shared target genes that were identified by expression correlation and cleavage site prediction. Multiple alignments were used to evaluate the putative targets to pinpoint the important residues for the substrate recognition. Finally, we validated our approach and identified biochemically PAPPA1 and ADAMTS6 as novel targets for FURIN proteolytic activity. Conclusions Most PCSK enzymes display strong positive expression correlation with predicted target proteins in our genome-wide analysis. We also show that expression correlation screen combined with a cleavage site-prediction analysis can be used to identify novel bona fide target molecules for PCSKs. Exploring the positively correlating genes can thus offer additional insights into the biology of proprotein convertases.

Published
2011
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14. Association of IL-10 and IL-10Rβ gene polymorphisms with graft-versus-host disease after haematopoietic stem cell transplantation from an HLA-identical sibling donor

Author

Volin Liisa, Turpeinen Hannu, Sivula Jyrki, and Partanen Jukka

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Extensive allelic matching in the human leukocyte antigen (HLA) genes is regarded as a prerequisite for good clinical success of allogeneic haematopoietic stem cell transplantation (HSCT). Also other genetic factors can be assumed to play a role in preventing and controlling the complications associated with allogeneic HSCT, in particular graft-versus-host disease (GvHD). Interleukin-10 (IL-10) and its receptor (IL-10R), key regulators of the immune response, are among these candidates. We studied the association of IL-10 and IL-10Rβ gene polymorphisms with the occurrence of GvHD in 309 HLA-identical sibling donor and recipient pairs. Results The difference in genotypic IL-10 production between patient and donor in combination with patient IL-10Rβ A/A genotype predisposed strongly to acute GvHD (OR = 7.15, p = 0.000023). On the other hand, a combination of same genotypic IL-10 production with patient IL-10Rβ A/A genotype protected from chronic GvHD (OR = 0.407, p = 0.0097). Conclusion Our results suggest that IL-10 and IL-10Rβ genes have a synergistic effect on the risk of GvHD.

Published
2009
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18. Multicenter analyses demonstrate significant clinical effects of minor Histocompatibility Antigens on GvHD and GvL after HLA-matched related and unrelated Hematopoietic stem cell transplantation

Author

UCL - (SLuc) Service d'hématologie, Spierings, Eric, Kim, Yeung-Hyen, Hendriks, Matthijs, Borst, Eric, Sergeant, Ruhena, Canossi, Angelica, Oudshoorn, Machteld, Loiseau, Pascale, Dolstra, Harry, Markiewicz, Miroslaw, Leffell, Mary S., Pereira, Noemi, Kircher, Brigitte, Turpeinen, Hannu, Eliaou, Jean-François, Gervais, Thibaut, Laurin, David, Enczmann, Jürgen, Martinetti, Miryam, Thomson, Jackie, Oguz, Fatma, Santarone, Stella, Partanen, Jukka, Siekiera, Urszula, Alessandrino, Emilio Paolo, Kalayoglu, Sevgi, Brand, Ronald, Goulmy, Els, UCL - (SLuc) Service d'hématologie, Spierings, Eric, Kim, Yeung-Hyen, Hendriks, Matthijs, Borst, Eric, Sergeant, Ruhena, Canossi, Angelica, Oudshoorn, Machteld, Loiseau, Pascale, Dolstra, Harry, Markiewicz, Miroslaw, Leffell, Mary S., Pereira, Noemi, Kircher, Brigitte, Turpeinen, Hannu, Eliaou, Jean-François, Gervais, Thibaut, Laurin, David, Enczmann, Jürgen, Martinetti, Miryam, Thomson, Jackie, Oguz, Fatma, Santarone, Stella, Partanen, Jukka, Siekiera, Urszula, Alessandrino, Emilio Paolo, Kalayoglu, Sevgi, Brand, Ronald, and Goulmy, Els

Abstract

The effect of minor H antigen mismatching on the occurrence of graft-versus-host disease (GvHD) and graft-versus-leukemia (GvL) after HLA-matched hematopoietic stem cell transplantation (HSCT) has mainly been demonstrated in single-center studies. Yet, the International Histocompatibility and Immunogenetics Workshops (IHIW) provide a collaborative platform to execute crucial large studies. In collaboration with 20 laboratories of the IHIW, the roles of 10 autosomal and 10 Y chromosome-encoded minor H antigens were investigated on GvHD and relapse incidence in 639 HLA-identical related donor (IRD) and 210 HLA-matched unrelated donor (MUD) HSCT recipients. Donor and recipient DNA samples were genotyped for the minor H antigens HA-1, HA-2, HA-3, HA-8, HB-1, ACC-1, ACC-2, SP110, PANE1, UGT2B17, and HY. The correlations with the primary outcomes GvHD (acute or chronic GvHD), survival, and relapse were statistically analyzed. The results of these multicenter analyses show that none of the HLA class I-restricted HY antigens were found to be associated with any of the primary outcomes. Interestingly, of the HLA class II-restricted HY antigens analyzed, HLA-DQ5 positive recipients showed a significantly increased GvHD-free survival in female-to-male HSCT compared with male-to-female HSCT (P= .013). Yet, analysis of the overall gender effect, thus independent of the known HY antigens, between the gender groups demonstrated an increased GvHD incidence in the female-to-male transplantations (P < .005) and a decreased GvHD-free survival in the female-to-male transplantations (P < .001). Of all autosomally encoded minor H antigens, only mismatching for the broadly expressed minor H antigen HA-8 increased the GvHD incidence in IRD HSCT (Hazard ratio [HR]= 5.28, P < .005), but not in MUD HSCT. Most striking was the influence of hematopoietic restricted minor H antigens on GvL as mismatching for hematopoietic minor H antigens correlated with lower relapse rates (P= .078), h

Published
2013

19. Proprotein Convertase Subtilisin/Kexin Type 7 (PCSK7) Is Essential for the Zebrafish Development and Bioavailability of Transforming Growth Factor β1a (TGFβ1a)

Author

Turpeinen, Hannu, primary, Oksanen, Anna, additional, Kivinen, Virpi, additional, Kukkurainen, Sampo, additional, Uusimäki, Annemari, additional, Rämet, Mika, additional, Parikka, Mataleena, additional, Hytönen, Vesa P., additional, Nykter, Matti, additional, and Pesu, Marko, additional

Published
2013
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21. Identification of proprotein convertase substrates using genome-wide expression correlation analysis

Author

University of Helsinki, Institute for Molecular Medicine Finland (FIMM), Turpeinen, Hannu, Kukkurainen, Sampo, Pulkkinen, Kati, Kauppila, Timo, Ojala, Kalle, Hytonen, Vesa P., Pesu, Marko, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), Turpeinen, Hannu, Kukkurainen, Sampo, Pulkkinen, Kati, Kauppila, Timo, Ojala, Kalle, Hytonen, Vesa P., and Pesu, Marko

Abstract

BACKGROUND: Subtilisin/kexin-like proprotein convertase (PCSK) enzymes have important regulatory function in a wide variety of biological processes. PCSKs proteolytically process at a target sequence that contains basic amino acids arginine and lysine, which results in functional maturation of the target protein. In vitro assays have showed significant biochemical redundancy between the seven family members, but the phenotypes of PCSK deficient mice and patients carrying an inactive PCSK allele argue for a specific biological function. Modeling the structures of individual PCSK enzymes has offered little insights into the specificity determinants. However, previous studies have shown that there can be a coordinated expression between a PCSK and its target molecule. Here, we have surveyed the putative PCSK target proteins using genome-wide expression correlation analysis and cleavage site prediction algorithms. RESULTS: We first performed a gene expression correlation analysis over the whole genome for all PCSK enzymes. PCSKs were found to cluster differently based on the strength of correlations. The screen for putative PCSK target proteins showed a significant enrichment (p-values from 1.2e-4 to <1.0e-10) of putative targets among the most positively correlating genes for most PCSKs. Interestingly, there was no enrichment in putative targets among the genes that correlated positively with the biologically redundant PCSK7, whereas PCSK5 showed an inverse correlation. PCSKs also showed a highly variable degree of shared target genes that were identified by expression correlation and cleavage site prediction. Multiple alignments were used to evaluate the putative targets to pinpoint the important residues for the substrate recognition. Finally, we validated our approach and identified biochemically PAPPA1 and ADAMTS6 as novel targets for FURIN proteolytic activity. CONCLUSIONS: Most PCSK enzymes display strong positive expression correlation with predicted t

Published
2011

22. Zebavidin - An Avidin-Like Protein from Zebrafish

Author

Taskinen, Barbara, primary, Zmurko, Joanna, additional, Ojanen, Markus, additional, Kukkurainen, Sampo, additional, Parthiban, Marimuthu, additional, Määttä, Juha A. E., additional, Leppiniemi, Jenni, additional, Jänis, Janne, additional, Parikka, Mataleena, additional, Turpeinen, Hannu, additional, Rämet, Mika, additional, Pesu, Marko, additional, Johnson, Mark S., additional, Kulomaa, Markku S., additional, Airenne, Tomi T., additional, and Hytönen, Vesa P., additional

Published
2013
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23. S-Layer Protein Mediates the Stimulatory Effect of Lactobacillus helveticus MIMLh5 on Innate Immunity

Author

Taverniti, Valentina, primary, Stuknyte, Milda, additional, Minuzzo, Mario, additional, Arioli, Stefania, additional, De Noni, Ivano, additional, Scabiosi, Christian, additional, Cordova, Zuzet Martinez, additional, Junttila, Ilkka, additional, Hämäläinen, Sanna, additional, Turpeinen, Hannu, additional, Mora, Diego, additional, Karp, Matti, additional, Pesu, Marko, additional, and Guglielmetti, Simone, additional

Published
2013
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24. Phenotype frequencies of autosomal minor histocompatibility antigens display significant differences among populations

Author

UCL - (SLuc) Service d'hématologie, Spierings, Eric, Hendriks, Matthijs, Absi, Léna, Canossi, Angelica, Chhaya, Sonal, Crowley, John, Dolstra, Harry, Eliaou, Jean-François, Ellis, Tom, Enczmann, Jürgen, Fasano, Maria E., Gervais, Thibaut, Gorodezky, Clara, Kircher, Brigitte, Laurin, David, Leffell, Mary S., Loiseau, Pascale, Malkki, Mari, Markiewicz, Miroslaw, Martinetti, Miryam, Maruya, Etsuko, Mehra, Narinder, Oguz, Fatma, Oudshoorn, Machteld, Pereira, Noemi, Rani, Rajni, Sergeant, Ruhena, Thomson, Jackie, Thuong, Hien Tran, Turpeinen, Hannu, Yang, Kuo-Liang, Zunec, Renata, Carrington, Mary, De Knijff, Peter, Goulmy, Els, UCL - (SLuc) Service d'hématologie, Spierings, Eric, Hendriks, Matthijs, Absi, Léna, Canossi, Angelica, Chhaya, Sonal, Crowley, John, Dolstra, Harry, Eliaou, Jean-François, Ellis, Tom, Enczmann, Jürgen, Fasano, Maria E., Gervais, Thibaut, Gorodezky, Clara, Kircher, Brigitte, Laurin, David, Leffell, Mary S., Loiseau, Pascale, Malkki, Mari, Markiewicz, Miroslaw, Martinetti, Miryam, Maruya, Etsuko, Mehra, Narinder, Oguz, Fatma, Oudshoorn, Machteld, Pereira, Noemi, Rani, Rajni, Sergeant, Ruhena, Thomson, Jackie, Thuong, Hien Tran, Turpeinen, Hannu, Yang, Kuo-Liang, Zunec, Renata, Carrington, Mary, De Knijff, Peter, and Goulmy, Els

Abstract

Minor histocompatibility (H) antigens are allogeneic target molecules having significant roles in alloimmune responses after human leukocyte antigen-matched solid organ and stem cell transplantation (SCT). Minor H antigens are instrumental in the processes of transplant rejection, graft-versus-host disease, and in the curative graft-versus-tumor effect of SCT. The latter characteristic enabled the current application of selected minor H antigens in clinical immunotherapeutic SCT protocols. No information exists on the global phenotypic distribution of the currently identified minor H antigens. Therefore, an estimation of their overall impact in human leukocyte antigen-matched solid organ and SCT in the major ethnic populations is still lacking. For the first time, a worldwide phenotype frequency analysis of ten autosomal minor H antigens was executed by 31 laboratories and comprised 2,685 randomly selected individuals from six major ethnic populations. Significant differences in minor H antigen frequencies were observed between the ethnic populations, some of which appeared to be geographically correlated.

Published
2007

25. SAP30L (Sin3A‐associated protein 30‐like) is involved in regulation of cardiac development and hematopoiesis in zebrafish embryos

Author

Teittinen, Kaisa J., primary, Grönroos, Toni, additional, Parikka, Mataleena, additional, Junttila, Sini, additional, Uusimäki, Annemari, additional, Laiho, Asta, additional, Korkeamäki, Hanna, additional, Kurppa, Kalle, additional, Turpeinen, Hannu, additional, Pesu, Marko, additional, Gyenesei, Attila, additional, Rämet, Mika, additional, and Lohi, Olli, additional

Published
2012
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26. In Vitro Functional and Immunomodulatory Properties of the Lactobacillus helveticus MIMLh5-Streptococcus salivarius ST3 Association That Are Relevant to the Development of a Pharyngeal Probiotic Product

Author

Taverniti, Valentina, primary, Minuzzo, Mario, additional, Arioli, Stefania, additional, Junttila, Ilkka, additional, Hämäläinen, Sanna, additional, Turpeinen, Hannu, additional, Mora, Diego, additional, Karp, Matti, additional, Pesu, Marko, additional, and Guglielmetti, Simone, additional

Published
2012
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27. Proprotein convertases in human atherosclerotic plaques: The overexpression of FURIN and its substrate cytokines BAFF and APRIL

Author

Turpeinen, Hannu, primary, Raitoharju, Emma, additional, Oksanen, Anna, additional, Oksala, Niku, additional, Levula, Mari, additional, Lyytikäinen, Leo-Pekka, additional, Järvinen, Otso, additional, Creemers, John W.M., additional, Kähönen, Mika, additional, Laaksonen, Reijo, additional, Pelto-Huikko, Markku, additional, Lehtimäki, Terho, additional, and Pesu, Marko, additional

Published
2011
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29. Narrower dilution block spacing of the headbox

Author

Turpeinen, Hannu, Teknillinen korkeakoulu, Helsinki University of Technology, Puunjalostustekniikan osasto, Paulapuro, Hannu, Leipälä, Matti, Turpeinen, Hannu, Teknillinen korkeakoulu, Helsinki University of Technology, Puunjalostustekniikan osasto, Paulapuro, Hannu, and Leipälä, Matti

Published
2003

31. Donor-recipient mismatch for common gene deletion polymorphisms in graft-versus-host disease

Author

McCarroll, Steven A, primary, Bradner, James E, additional, Turpeinen, Hannu, additional, Volin, Liisa, additional, Martin, Paul J, additional, Chilewski, Shannon D, additional, Antin, Joseph H, additional, Lee, Stephanie J, additional, Ruutu, Tapani, additional, Storer, Barry, additional, Warren, Edus H, additional, Zhang, Bo, additional, Zhao, Lue Ping, additional, Ginsburg, David, additional, Soiffer, Robert J, additional, Partanen, Jukka, additional, Hansen, John A, additional, Ritz, Jerome, additional, Palotie, Aarno, additional, and Altshuler, David, additional

Published
2009
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34. Phenotype Frequencies of Autosomal Minor Histocompatibility Antigens Display Significant Differences among Populations

Author

Spierings, Eric, primary, Hendriks, Matthijs, additional, Absi, Léna, additional, Canossi, Angelica, additional, Chhaya, Sonal, additional, Crowley, John, additional, Dolstra, Harry, additional, Eliaou, Jean-François, additional, Ellis, Tom, additional, Enczmann, Jürgen, additional, Fasano, Maria E, additional, Gervais, Thibaut, additional, Gorodezky, Clara, additional, Kircher, Brigitte, additional, Laurin, David, additional, Leffell, Mary S, additional, Loiseau, Pascale, additional, Malkki, Mari, additional, Markiewicz, Miroslaw, additional, Martinetti, Miryam, additional, Maruya, Etsuko, additional, Mehra, Narinder, additional, Oguz, Fatma, additional, Oudshoorn, Machteld, additional, Pereira, Noemi, additional, Rani, Rajni, additional, Sergeant, Ruhena, additional, Thomson, Jackie, additional, Tran, Thuong Hien, additional, Turpeinen, Hannu, additional, Yang, Kuo-Liang, additional, Zunec, Renata, additional, Carrington, Mary, additional, de Knijff, Peter, additional, and Goulmy, Els, additional

Published
2007
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36. Vitamin D receptor polymorphisms: no association with type 1 diabetes in the Finnish population.

Author

Turpeinen, Hannu, Hermann, Robert, Vaara, Satu, Laine, Antti-Pekka, Simell, Olli, Knip, Mikael, Veijola, Riitta, and Ilonen, Jorma

Abstract

OBJECTIVE: The effect of polymorphisms of the vitamin D receptor (VDR) gene on susceptibility to type 1 diabetes has recently been investigated extensively. Several findings on positive disease associations have been observed and, in addition, a protective effect of vitamin D supplementation has been reported. DESIGN: We studied the effect of three vitamin D receptor gene polymorphisms (VDRA, VDRB, VDRF) on susceptibility to type 1 diabetes in a large case-control series (more than 2000 controls and about 1000 patients) from the Finnish population. METHODS: A combination of case-control and affected-family based approaches was used. Subjects were genotyped for VDRA (ApaI), VDRB (BsmI) and VDRF (FokI) single nucleotide polymorphisms using a minisequencing reaction. RESULTS: A few borderline significant associations were observed with both approaches used. In the case-control association analyses we found significant differences between cases and controls in frequencies of VDRB (P=0.024, all subjects and P=0.016, HLA DQB1*0302-positive subjects) and VDRF (P=0.0063, Turku cohort). In the total family set a decreased (39.3%) transmission of the VDRA-VDRB-VDRF haplotype 1-1-2 and an increased (60.3%) transmission of haplotype 2-1-2 to sons was seen (P=0.0059 and P=0.024 respectively). Transmission of the haplotype 2-2-1 to daughters was decreased (37.6%, P=0.022). Interestingly, we also observed significant differences in allele frequencies of the polymorphisms studied between populations from three different regions in Finland. CONCLUSIONS: All these differences disappeared after correction for multiple testing. We conclude that the single nucleotide polymorphisms analysed are unlikely to be associated with type 1 diabetes in the Finnish population.

Published
2003

37. Genetic similarity of chromosome 6 between patients receiving hematopoietic stem cell transplantation and HLA matched sibling donors.

Author

Turpeinen H, Volin L, Nikkinen L, Ojala P, Palotie A, Saarela J, and Partanen J

Subjects
HLA Antigens genetics, Histocompatibility Testing methods, Humans, Polymorphism, Single Nucleotide, Siblings, Tissue Donors, Chromosomes, Human, Pair 6 genetics, Hematopoietic Stem Cell Transplantation methods, Histocompatibility genetics
Abstract

Background: Matching for HLA genes located on chromosome 6 is required in hematopoietic stem cell transplantation to reduce the incidence of graft-versus-host disease. However, a considerable proportion of patients still suffer from it, obviously due to genetic differences outside the HLA gene region., Design and Methods: We studied the similarity of almost 4,000 single nucleotide polymorphisms on chromosome 6 between patients receiving hematopoietic stem cell transplantation and their HLA-matched sibling donors., Results: We observed that as a result of routine HLA matching the siblings in fact shared surprisingly long chromosomal fragments with similar single nucleotide polymorphism genotypes--from 11.65 Mb to 134.66 Mb. The number of genes mapped on these shared fragments varied from 402 to 1,302. Considering the whole chromosome 6, the HLA-matched siblings were apparently identical for 65.2-97.8% of the single nucleotide polymorphisms., Conclusions: Potentially, genes similar in some transplantation pairs while different in others might have a significant role in determining the outcome after hematopoietic stem cell transplantation.

Published
2009
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