Browsing by Subject "COPY-NUMBER VARIATION"

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  • Liesmaa, Inka; Paakkanen, Riitta; Järvinen, Asko; Valtonen, Ville; Lokki, Marja-Liisa (2018)
    Introduction Homozygous deficiencies of complement C4A or C4B are detected in 1-10% of populations. In genome-wide association studies C4 deficiencies are missed because the genetic variation of C4 is complex. There are no studies where the clinical presentation of these patients is analyzed. This study was aimed to characterize the clinical features of patients with homozygous C4A or C4B deficiency. Material and methods Thirty-two patients with no functional C4A, 87 patients with no C4B and 120 with normal amount of C4 genes were included. C4A and C4B numbers were assessed with genomic quantitative real-time PCR. Medical history was studied retrospectively from patients' files. Results Novel associations between homozygous C4A deficiency and lymphoma, coeliac disease and sarcoidosis were detected. These conditions were present in 12.5%, (4/32 in patients vs. 0.8%, 1/120, in controls, OR = 17.00, 95%Cl = 1.83-158.04, p = 0.007), 12.5% (4/32 in patients vs. 0%, 0/120 in controls, OR = 1.14, 95%Cl = 1.00-1.30, p = 0.002) and 12.5%, respectively (4/32 in patients vs. 2.5%, 3/120 in controls, OR = 5.571, 95%Cl = 1.79-2.32, p = 0.036). In addition, C4A and C4B deficiencies were both associated with adverse drug reactions leading to drug discontinuation (34.4%, 11/32 in C4A-deficient patients vs. 14.2%, 17/120 in controls, OR = 3.174, 95%Cl = 1.30-7.74, p = 0.009 and 28.7%, 25/87 in C4B-deficient patients, OR = 2.44, 95%Cl = 1.22-4.88, p = 0.010). Conclusion This reported cohort of homozygous deficiencies of C4A or C4B suggests that C4 deficiencies may have various unrecorded disease associations. C4 gene should be considered as a candidate gene in studying these selected disease associations.
  • 99Lives Consortium; Genova, F.; Lohi, Hannes (2018)
    BackgroundCopy Number Variations (CNVs) have becoming very significant variants, representing a major source of genomic variation. CNVs involvement in phenotypic expression and different diseases has been widely demonstrated in humans as well as in many domestic animals. However, genome wide investigation on these structural variations is still missing in Felis catus. The present work is the first CNV mapping from a large data set of Next Generation Sequencing (NGS) data in the domestic cat, performed within the 99 Lives Consortium.ResultsReads have been mapped on the reference assembly_6.2 by Maverix Biomics. CNV detection with cn.MOPS and CNVnator detected 592 CNVs. These CNVs were used to obtain 154 CNV Regions (CNVRs) with BedTools, including 62 singletons. CNVRs covered 0.26% of the total cat genome with 129 losses, 19 gains and 6 complexes. Cluster Analysis and Principal Component Analysis of the detected CNVRs showed that breeds tend to cluster together as well as cats sharing the same geographical origins. The 46 genes identified within the CNVRs were annotated.ConclusionThis study has improved the genomic characterization of 14 cat breeds and has provided CNVs information that can be used for studies of traits in cats. It can be considered a sound starting point for genomic CNVs identification in this species.
  • Leblond, Claire S.; Heinrich, Jutta; Delorme, Richard; Proepper, Christian; Betancur, Catalina; Huguet, Guillaume; Konyukh, Marina; Chaste, Pauline; Ey, Elodie; Rastam, Maria; Anckarsater, Henrik; Nygren, Gudrun; Gillberg, I. Carina; Melke, Jonas; Toro, Roberto; Regnault, Beatrice; Fauchereau, Fabien; Mercati, Oriane; Lemiere, Nathalie; Skuse, David; Poot, Martin; Holt, Richard; Monaco, Anthony P.; Jarvela, Irma; Kantojärvi, Katri; Vanhala, Raija; Curran, Sarah; Collier, David A.; Bolton, Patrick; Chiocchetti, Andreas; Klauck, Sabine M.; Poustka, Fritz; Freitag, Christine M.; Waltes, Regina; Kopp, Marnie; Duketis, Eftichia; Bacchelli, Elena; Minopoli, Fiorella; Ruta, Liliana; Battaglia, Agatino; Mazzone, Luigi; Maestrini, Elena; Sequeira, Ana F.; Oliveira, Barbara; Vicente, Astrid; Oliveira, Guiomar; Pinto, Dalila; Scherer, Stephen W.; Zelenika, Diana; Delepine, Marc; Lathrop, Mark; Bonneau, Dominique; Guinchat, Vincent; Devillard, Francoise; Assouline, Brigitte; Mouren, Marie-Christine; Leboyer, Marion; Gillberg, Christopher; Boeckers, Tobias M.; Bourgeron, Thomas (2012)