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Hube Pausch - One of the best experts on this subject based on the ideXlab platform.
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assessing genomic diversity and signatures of selection in original braunvieh cattle using whole genome sequencing data
BMC Genomics, 2020Co-Authors: Meenu Hati, Danang Crysnanto, Naveen Kuma Kadri, Hube PauschAbstract:Autochthonous cattle breeds are an important source of genetic variation because they might carry alleles that enable them to adapt to local environment and food conditions. Original Braunvieh (OB) is a local cattle breed of Switzerland used for beef and milk production in alpine areas. Using whole-genome sequencing (WGS) data of 49 key ancestors, we characterize genomic diversity, genomic inbreeding, and signatures of selection in Swiss OB cattle at nucleotide resolution. We annotated 15,722,811 SNPs and 1,580,878 Indels including 10,738 and 2763 missense deleterious and high impact variants, respectively, that were discovered in 49 OB key ancestors. Six Mendelian trait-associated variants that were previously detected in breeds other than OB, segregated in the sequenced key ancestors including variants causal for recessive Xanthinuria and albinism. The average nucleotide diversity (1.6 × 10− 3) was higher in OB than many mainstream European cattle breeds. Accordingly, the average genomic inbreeding derived from runs of homozygosity (ROH) was relatively low (FROH = 0.14) in the 49 OB key ancestor animals. However, genomic inbreeding was higher in OB cattle of more recent generations (FROH = 0.16) due to a higher number of long (> 1 Mb) runs of homozygosity. Using two complementary approaches, composite likelihood ratio test and integrated haplotype score, we identified 95 and 162 genomic regions encompassing 136 and 157 protein-coding genes, respectively, that showed evidence (P < 0.005) of past and ongoing selection. These selection signals were enriched for quantitative trait loci related to beef traits including meat quality, feed efficiency and body weight and pathways related to blood coagulation, nervous and sensory stimulus. We provide a comprehensive overview of sequence variation in Swiss OB cattle genomes. With WGS data, we observe higher genomic diversity and less inbreeding in OB than many European mainstream cattle breeds. Footprints of selection were detected in genomic regions that are possibly relevant for meat quality and adaptation to local environmental conditions. Considering that the population size is low and genomic inbreeding increased in the past generations, the implementation of optimal mating strategies seems warranted to maintain genetic diversity in the Swiss OB cattle population.
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assessing genomic diversity and signatures of selection in original braunvieh cattle using whole genome sequencing data
bioRxiv, 2019Co-Authors: Meenu Hati, Danang Crysnanto, Naveen Kuma Kadri, Hube PauschAbstract:Background: Autochthonous cattle breeds represent an important source of genetic variation because they might carry alleles that enable them to adapt to local environment and food conditions. Original Braunvieh (OB) is a local cattle breed of Switzerland used for beef and milk production in alpine areas. Using whole-genome sequencing (WGS) data of 49 key ancestors, we characterize genomic diversity, genomic inbreeding, and signatures of selection in Swiss OB cattle at nucleotide resolution. Results: We annotated 15,722,811 million SNPs and 1,580,878 million Indels including 10,738 and 2,763 missense deleterious and high impact variants, respectively, that were discovered in 49 OB key ancestors. Six Mendelian trait-associated variants that were previously detected in breeds other than OB, segregated in the sequenced key ancestors including variants causal for recessive Xanthinuria and albinism. The average nucleotide diversity (1.6 × 10−3) was higher in OB than many mainstream European cattle breeds. Accordingly, the average genomic inbreeding quantified using runs of homozygosity (ROH) was relatively low (FROH=0.14) in the 49 OB key ancestor animals. However, genomic inbreeding was higher in more recent generations of OB cattle (FROH=0.16) due to a higher number of long (> 1 Mb) runs of homozygosity. Using two complementary approaches, composite likelihood ratio test and integrated haplotype score, we identified 95 and 162 genomic regions encompassing 136 and 157 protein-coding genes, respectively, that showed evidence (P
Kimiyoshi Ichida - One of the best experts on this subject based on the ideXlab platform.
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a case of Xanthinuria type i with a novel mutation in xanthine dehydrogenase
CEN Case Reports, 2016Co-Authors: Akira Iguchi, Takaaki Sato, Mihoko Yamazaki, Kazuyuki Tasaki, Yasushi Suzuki, Noriaki Iino, Hiroshi Hasegawa, Kimiyoshi Ichida, Ichiei NaritaAbstract:Hereditary hypouricemia is generally caused by renal hypouricemia, an autosomal recessive disorder that is characterized by impaired renal tubular uric acid transport, or by Xanthinuria, a rare autosomal recessive disorder caused by a deficiency of xanthine dehydrogenase (XDH; Xanthinuria type I) or by a deficiency of both XDH and aldehyde oxidase (Xanthinuria type II). In contrast to renal hypouricemia, which sometimes leads to exercise-induced acute kidney injury (EIAKI), Xanthinuria has not been associated with this disorder. We report here a case of Xanthinuria type I due to a compound heterozygous mutation. A 46-year-old woman was found to have undetectable plasma and urinary levels of uric acid. She had no symptoms and no history of EIAKI. Xanthinuria type I was diagnosed following the allopurinol loading test. Mutation analysis revealed a compound heterozygous mutation [c.305A>G (p.Gln102Arg) and c.2567delC (p.Thr856Lysfs*73)] in the XDH gene. Of these two mutations, the former is novel. The patient did not exhibit EIAKI. However, because Xanthinuria is a rare disease, the identification of additional cases is necessary to determine whether this disease is complicated with EIAKI.
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identification of a Xanthinuria type i case with mutations of xanthine dehydrogenase in an afghan child
Clinica Chimica Acta, 2012Co-Authors: Makiko Nakamura, Yamaguchi Yuichiro, Jorn Oliver Sass, Matsumura Tomohiro, Karl Otfried Schwab, Nishino Takeshi, Hosoya Tatsuo, Kimiyoshi IchidaAbstract:Xanthinuria due to xanthine dehydrogenase (XDH) deficiency is a rare genetic disorder characterized by hypouricemia and the accumulation of xanthine in the urine. We have identified an Afghan girl whose Xanthinuria could be classified as type I Xanthinuria based on an allopurinol loading test. Three mutations were identified in the XDH gene, 141insG, C2729T (T910M) and C3886T (R1296W). Site-directed mutagenesis followed by expression analysis in Escherichia coli revealed that not only the frame shift mutation 141insG impairs XDH activity, but also the missense mutation C2729T, while C3886T resulted in major residual activity of about 50% of the wild type. In this report, a case of Xanthinuria type I with mutations of XDH was identified and characterized by expression studies.
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Mutations Associated with Functional Disorder of Xanthine Oxidoreductase and Hereditary Xanthinuria in Humans
2012Co-Authors: Kimiyoshi Ichida, Yoshihiro Amaya, Ken Okamoto, Takeshi NishinoAbstract:Abstract: Xanthine oxidoreductase (XOR) catalyzes the conversion of hypoxanthine to xanthine and xanthine to uric acid with concomitant reduction of either NAD + or O2. The enzyme is a target of drugs to treat hyperuricemia, gout and reactive oxygen-related diseases. Human diseases associated with genetically determined dysfunction of XOR are termed Xanthinuria, because of the excretion of xanthine in urine. Xanthinuria is classified into two subtypes, type I and type II. Type I Xanthinuria involves XOR deficiency due to genetic defect of XOR, whereas type II Xanthinuria involves dual deficiency of XOR and aldehyde oxidase (AO, a molybdoflavo enzyme similar to XOR) due to genetic defect in the molybdenum cofactor sulfurase. Molybdenum cofactor deficiency is associated with triple deficiency of XOR, AO and sulfite oxidase, due to defective synthesis of molybdopterin, which is a precursor of molybdenum cofactor for all three enzymes. The present review focuses on mutation or chemical modification studies of mammalian XOR, as well as on XOR mutations identified in humans, aimed at understanding the reaction mechanism of XOR and the relevance of mutated XORs as models to estimate the possibl
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Mutations Associated with Functional Disorder of Xanthine Oxidoreductase and Hereditary Xanthinuria in Humans
MDPI AG, 2012Co-Authors: Takeshi Nishino, Kimiyoshi Ichida, Ken Okamoto, Yoshihiro AmayaAbstract:Xanthine oxidoreductase (XOR) catalyzes the conversion of hypoxanthine to xanthine and xanthine to uric acid with concomitant reduction of either NAD+ or O2. The enzyme is a target of drugs to treat hyperuricemia, gout and reactive oxygen-related diseases. Human diseases associated with genetically determined dysfunction of XOR are termed Xanthinuria, because of the excretion of xanthine in urine. Xanthinuria is classified into two subtypes, type I and type II. Type I Xanthinuria involves XOR deficiency due to genetic defect of XOR, whereas type II Xanthinuria involves dual deficiency of XOR and aldehyde oxidase (AO, a molybdoflavo enzyme similar to XOR) due to genetic defect in the molybdenum cofactor sulfurase. Molybdenum cofactor deficiency is associated with triple deficiency of XOR, AO and sulfite oxidase, due to defective synthesis of molybdopterin, which is a precursor of molybdenum cofactor for all three enzymes. The present review focuses on mutation or chemical modification studies of mammalian XOR, as well as on XOR mutations identified in humans, aimed at understanding the reaction mechanism of XOR and the relevance of mutated XORs as models to estimate the possible side effects of clinical application of XOR inhibitors
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mutational analysis of the xanthine dehydrogenase gene in a turkish family with autosomal recessive classical Xanthinuria
Nephrology Dialysis Transplantation, 2003Co-Authors: Faysal Gok, Kimiyoshi Ichida, Rezan TopalogluAbstract:Background. Classical Xanthinuria is classified into two categories: type I, deficient only in xanthine dehydrogenase (XDH) activity; and type II, deficient in both XDH and aldehyde oxidase. Both types present mainly with renal stones and lead to renal failure in some cases. We studied the molecular basis of Xanthinuria in a Turkish family with two affected siblings. Methods. We examined two brothers aged 1 and 14 years who presented with histories of passing several urinary stones. We measured their serum and urine levels of uric acid and oxypurine, chemically analysed their stones and performed allopurinol loading tests to diagnose the type of Xanthinuria. In addition, we studied the coding regions of the XDH gene in family members. Results. In the siblings, serum uric acid was undetectable and serum oxypurine was elevated. Laboratory studies showed that the stones that they passed were composed of xanthine, and both were diagnosed as having classical Xanthinuria. The allopurinol loading tests indicated their Xanthinuria to be type I. Within the entire coding region of the XDH gene, an A to T base change at nucleotide position 2164 was identified in the siblings, indicating a nonsense substitution from AAG (Lys) to TAG (Tyr) at codon 722. Concerning this novel nonsense mutation, restriction fragment length polymorphism (RFLP) analysis showed that the brothers were both homozygous, while the parents were heterozygous, and this confirmed the autosomal recessive inheritance of the XDH gene mutation. Conclusions. In a Turkish family, we identified a novel point mutation in the XDH gene responsible for classical type I Xanthinuria. That both parents had a history of passing renal stones in spite of being heterozygous for that mutation may indicate that individuals with a heterozygous nonsense XDH mutation are more susceptible to nephrolithiasis than healthy individuals. This raises the point that individuals with a heterozygous XDH mutation may also present with renal stones.
Danang Crysnanto - One of the best experts on this subject based on the ideXlab platform.
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Assessing genomic diversity and signatures of selection in Original Braunvieh cattle using whole-genome sequencing data
BMC Genomics, 2020Co-Authors: Meenu Bhati, Naveen Kumar Kadri, Danang Crysnanto, Hubert PauschAbstract:Background Autochthonous cattle breeds are an important source of genetic variation because they might carry alleles that enable them to adapt to local environment and food conditions. Original Braunvieh (OB) is a local cattle breed of Switzerland used for beef and milk production in alpine areas. Using whole-genome sequencing (WGS) data of 49 key ancestors, we characterize genomic diversity, genomic inbreeding, and signatures of selection in Swiss OB cattle at nucleotide resolution. Results We annotated 15,722,811 SNPs and 1,580,878 Indels including 10,738 and 2763 missense deleterious and high impact variants, respectively, that were discovered in 49 OB key ancestors. Six Mendelian trait-associated variants that were previously detected in breeds other than OB, segregated in the sequenced key ancestors including variants causal for recessive Xanthinuria and albinism. The average nucleotide diversity (1.6 × 10^− 3) was higher in OB than many mainstream European cattle breeds. Accordingly, the average genomic inbreeding derived from runs of homozygosity (ROH) was relatively low (F_ROH = 0.14) in the 49 OB key ancestor animals. However, genomic inbreeding was higher in OB cattle of more recent generations (F_ROH = 0.16) due to a higher number of long (> 1 Mb) runs of homozygosity. Using two complementary approaches, composite likelihood ratio test and integrated haplotype score, we identified 95 and 162 genomic regions encompassing 136 and 157 protein-coding genes, respectively, that showed evidence ( P
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assessing genomic diversity and signatures of selection in original braunvieh cattle using whole genome sequencing data
BMC Genomics, 2020Co-Authors: Meenu Hati, Danang Crysnanto, Naveen Kuma Kadri, Hube PauschAbstract:Autochthonous cattle breeds are an important source of genetic variation because they might carry alleles that enable them to adapt to local environment and food conditions. Original Braunvieh (OB) is a local cattle breed of Switzerland used for beef and milk production in alpine areas. Using whole-genome sequencing (WGS) data of 49 key ancestors, we characterize genomic diversity, genomic inbreeding, and signatures of selection in Swiss OB cattle at nucleotide resolution. We annotated 15,722,811 SNPs and 1,580,878 Indels including 10,738 and 2763 missense deleterious and high impact variants, respectively, that were discovered in 49 OB key ancestors. Six Mendelian trait-associated variants that were previously detected in breeds other than OB, segregated in the sequenced key ancestors including variants causal for recessive Xanthinuria and albinism. The average nucleotide diversity (1.6 × 10− 3) was higher in OB than many mainstream European cattle breeds. Accordingly, the average genomic inbreeding derived from runs of homozygosity (ROH) was relatively low (FROH = 0.14) in the 49 OB key ancestor animals. However, genomic inbreeding was higher in OB cattle of more recent generations (FROH = 0.16) due to a higher number of long (> 1 Mb) runs of homozygosity. Using two complementary approaches, composite likelihood ratio test and integrated haplotype score, we identified 95 and 162 genomic regions encompassing 136 and 157 protein-coding genes, respectively, that showed evidence (P < 0.005) of past and ongoing selection. These selection signals were enriched for quantitative trait loci related to beef traits including meat quality, feed efficiency and body weight and pathways related to blood coagulation, nervous and sensory stimulus. We provide a comprehensive overview of sequence variation in Swiss OB cattle genomes. With WGS data, we observe higher genomic diversity and less inbreeding in OB than many European mainstream cattle breeds. Footprints of selection were detected in genomic regions that are possibly relevant for meat quality and adaptation to local environmental conditions. Considering that the population size is low and genomic inbreeding increased in the past generations, the implementation of optimal mating strategies seems warranted to maintain genetic diversity in the Swiss OB cattle population.
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assessing genomic diversity and signatures of selection in original braunvieh cattle using whole genome sequencing data
bioRxiv, 2019Co-Authors: Meenu Hati, Danang Crysnanto, Naveen Kuma Kadri, Hube PauschAbstract:Background: Autochthonous cattle breeds represent an important source of genetic variation because they might carry alleles that enable them to adapt to local environment and food conditions. Original Braunvieh (OB) is a local cattle breed of Switzerland used for beef and milk production in alpine areas. Using whole-genome sequencing (WGS) data of 49 key ancestors, we characterize genomic diversity, genomic inbreeding, and signatures of selection in Swiss OB cattle at nucleotide resolution. Results: We annotated 15,722,811 million SNPs and 1,580,878 million Indels including 10,738 and 2,763 missense deleterious and high impact variants, respectively, that were discovered in 49 OB key ancestors. Six Mendelian trait-associated variants that were previously detected in breeds other than OB, segregated in the sequenced key ancestors including variants causal for recessive Xanthinuria and albinism. The average nucleotide diversity (1.6 × 10−3) was higher in OB than many mainstream European cattle breeds. Accordingly, the average genomic inbreeding quantified using runs of homozygosity (ROH) was relatively low (FROH=0.14) in the 49 OB key ancestor animals. However, genomic inbreeding was higher in more recent generations of OB cattle (FROH=0.16) due to a higher number of long (> 1 Mb) runs of homozygosity. Using two complementary approaches, composite likelihood ratio test and integrated haplotype score, we identified 95 and 162 genomic regions encompassing 136 and 157 protein-coding genes, respectively, that showed evidence (P
Hubert Pausch - One of the best experts on this subject based on the ideXlab platform.
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Assessing genomic diversity and signatures of selection in Original Braunvieh cattle using whole-genome sequencing data
BMC Genomics, 2020Co-Authors: Meenu Bhati, Naveen Kumar Kadri, Danang Crysnanto, Hubert PauschAbstract:Background Autochthonous cattle breeds are an important source of genetic variation because they might carry alleles that enable them to adapt to local environment and food conditions. Original Braunvieh (OB) is a local cattle breed of Switzerland used for beef and milk production in alpine areas. Using whole-genome sequencing (WGS) data of 49 key ancestors, we characterize genomic diversity, genomic inbreeding, and signatures of selection in Swiss OB cattle at nucleotide resolution. Results We annotated 15,722,811 SNPs and 1,580,878 Indels including 10,738 and 2763 missense deleterious and high impact variants, respectively, that were discovered in 49 OB key ancestors. Six Mendelian trait-associated variants that were previously detected in breeds other than OB, segregated in the sequenced key ancestors including variants causal for recessive Xanthinuria and albinism. The average nucleotide diversity (1.6 × 10^− 3) was higher in OB than many mainstream European cattle breeds. Accordingly, the average genomic inbreeding derived from runs of homozygosity (ROH) was relatively low (F_ROH = 0.14) in the 49 OB key ancestor animals. However, genomic inbreeding was higher in OB cattle of more recent generations (F_ROH = 0.16) due to a higher number of long (> 1 Mb) runs of homozygosity. Using two complementary approaches, composite likelihood ratio test and integrated haplotype score, we identified 95 and 162 genomic regions encompassing 136 and 157 protein-coding genes, respectively, that showed evidence ( P
Ivan Sebesta - One of the best experts on this subject based on the ideXlab platform.
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hereditary Xanthinuria is not so rare disorder of purine metabolism
Nucleosides Nucleotides & Nucleic Acids, 2018Co-Authors: Ivan Sebesta, Blanka Stiburkova, Jakub KrijtAbstract:Hereditary Xanthinuria (type I) is caused by an inherited deficiency of the xanthine oxidorectase (XDH/XO), and is characterized by very low concentration of uric acid in blood and urine and high concentration of urinary xanthine, leading to urolithiasis. Type II results from a combined deficiency of XDH/XO and aldehyde oxidase. Patients present with hematuria, renal colic, urolithiasis or even acute renal failure. Clinical symptoms are the same for both types. In a third type, clinically distinct, sulfite oxidase activity is missing as well as XDH/XO and aldehyde oxidase. The prevalence is not known, but about 150 cases have been described so far. Hypouricemia is sometimes overlooked, that´s why we have set up the diagnostic flowchart. This consists of a) evaluation of uric acid concentrations in serum and urine with exclusion of primary renal hypouricemia, b) estimation of urinary xanthine, c) allopurinol loading test, which enables to distinguish type I and II; and finally assay of xanthine oxidoreductase activity in plasma with molecular genetic analysis. Following this diagnostic procedure we were able to find first patients with hereditary Xanthinuria in our Czech population. We have detected nine cases, which is one of the largest group worldwide. Four patients were asymptomatic. All had profound hypouricemia, which was the first sign and led to referral to our department. Urinary concentrations of xanthine were in the range of 170-598 mmol/mol creatinine (normal < 30 mmol/mol creatinine). Hereditary Xanthinuria is still unrecognized disorder and subjects with unexplained hypouricemia need detailed purine metabolic investigation.
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novel mutations in xanthine dehydrogenase oxidase cause severe hypouricemia biochemical and molecular genetic analysis in two czech families with Xanthinuria type i
Clinica Chimica Acta, 2012Co-Authors: Blanka Stiburkova, Jakub Krijt, Petr Vyletal, Josef Bartl, Eva Gerhatova, Martin Korinek, Ivan SebestaAbstract:Abstract Background The article describes the clinical, biochemical, enzymological and molecular genetics findings in two patients from two families with Xanthinuria type I. Methods Biochemical analysis using high performance liquid chromatography, allopurinol loading test and analysis of xanthine oxidase activity in plasma and of uromodulin excretion in urine were performed. Sequencing analysis of the xanthine dehydrogenase gene and the haplotype and statistical analyses of consanguinity were performed. Results Probands showed extremely low concentrations of uric acid, on seven occasions under the limit of detection. The concentration of uric acid in 38-year-old female was 15 μmol/L in serum and 0.04 mmol/L in urine. Excretion of xanthine in urine was 170 mmol/mol creatinine. The concentration of uric acid in 25-year-old male was 0.03 mmol/L in urine. Excretion of xanthine in urine was 141 mmol/mol creatinine. The allopurinol loading test confirmed Xanthinuria type I. The xanthine oxidase activities in patients were 0 and 0.4 pmol/h/mL of plasma. We found three nonsense changes: p.P214QfsX4 and unpublished p.R825X and p.R881X. Conclusions We found two nonconsanguineous compound heterozygotes with Xanthinuria type I caused by three nonsense changes. The methods used did not confirm consanguinity in the probands, thus there might be an unconfirmed biological relationship or mutational hotspot.
