The Experts below are selected from a list of 18654 Experts worldwide ranked by ideXlab platform
Hiroshi Kimura - One of the best experts on this subject based on the ideXlab platform.
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two distinct alu mediated deletions of the human abo secretor fut2 locus in samoan and bangladeshi populations
Human Mutation, 2000Co-Authors: Hao Pang, Mikiko Soejima, Yoshiro Koda, Noboru Fujitani, Mohammed Nasimul Islam, A Shamsul K M Islam, Hiroshi KimuraAbstract:The human secretor α(1,2) fucosyltransferase encoded by the FUT2 determines the production of ABO(H) antigens in secretions. Recent studies demonstrated the presence of several nonfunctional Alleles in the FUT2. During the analysis for inactivating mutations at the FUT2 locus from 24 Samoan and 47 Bangladeshi individuals, we found two distinct Alu-mediated deletions of FUT2. The FUT2 deletion in a Bangladeshi population was identical with that found in Indian individuals with the Bombay phenotype (sedel), but not associated with the Null Allele (T725G) of the H gene (FUT1). The FUT2 deletion in Samoans is a novel Null Allele (sedel2). The junction region of sedel2 was successfully amplified using the same primers for the sedel amplification. DNA sequencing of the junction region of the sedel2 indicated that there was a 32-bp sequence identity between DNA sequences surrounding the 5′ and 3′ breakpoints. The size of the deletion of the sedel2 was 9.3 kb, including the full coding region of FUT2. The frequency of the sedel in a Bangladeshi population was 0.074, and that of the sedel2 in a Samoan population was 0.104. Hum Mutat 16:274, 2000. © 2000 Wiley-Liss, Inc.
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ancient origin of the Null Allele se 428 of the human abo secretor locus fut2
Journal of Molecular Evolution, 2000Co-Authors: Yoshiro Koda, Mikiko Soejima, Hidenori Tachida, Osamu Takenaka, Hiroshi KimuraAbstract:In human populations, a Null Allele having several nucleotide differences from the wild-type Allele is segregating at the FUT2 locus (the ABO-Secretor locus) encoding alpha(1,2)fucosyltransferase. To estimate the age of the most recent common ancestor (MRCA) of these two Alleles, we sequenced FUT2 homologues from chimpanzee, gorilla, orangutan, and green monkey. Since we did not detect acceleration or any heterogeneity in the substitution rate at this locus among these species, the age of the MRCA was estimated to be around 3 MYA, assuming the divergence time of human and chimpanzee to be 5 MYA. We developed a simple test to examine whether or not the old age of the MRCA of the FUT2 is consistent with that expected for two divergent neutral Alleles sampled from a random mating population. An application of the test to the data at FUT2 indicated that the age of the MRCA is too old to be explained by the simple neutral assumptions, although our test depends on accurate estimation of the divergence time of human and chimpanzee in units of twice the human population size. Various possibilities including balancing selection are discussed to explain this old age of the MRCA.
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The Fusion Gene at the ABO-Secretor Locus ( FUT2 ): absence in Chinese populations
Journal of Human Genetics, 1999Co-Authors: Yoshiro Koda, Bao-jie Wang, Heung Bum Oh, Mikiko Soejima, Hao Pang, Hiroshi KimuraAbstract:The fusion gene (sefus) is a Null Allele of the secretor type α (1, 2) fucosyltransferase gene (FUT2) and was first found in a Japanese population. It has not yet been reported in any other ethnic population. In the present study, we investigated the distribution of the fusion gene of the FUT2 locus in five populations from three ethnic groups in East Asia. The fusion gene was found in two additional Japanese populations with a high frequency (0.0551 in Okinawa and 0.0792 in Akita) and, for the first time outside Japan, in a Korean population, at a very low frequency (0.0063 in Seoul). In contrast, we found no fusion gene in two Chinese populations. These findings showed that the FUT2 fusion gene was ubiquitous in Japanese, but was rare in neighboring populations, suggesting that the FUT2 fusion gene had emerged from within the Japanese. Additionally, a new Null Allele with a C-to-T substitution at nucleotide 658 was found in one individual native of southern China.
Stephen A Osmani - One of the best experts on this subject based on the ideXlab platform.
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identification and analysis of essential aspergillus nidulans genes using the heterokaryon rescue technique
Nature Protocols, 2006Co-Authors: Aysha H Osmani, Berl R Oakley, Stephen A OsmaniAbstract:In the heterokaryon rescue technique, gene deletions are carried out using the pyrG nutritional marker to replace the coding region of target genes via homologous recombination in Aspergillus nidulans. If an essential gene is deleted, the Null Allele is maintained in spontaneously generated heterokaryons that consist of two genetically distinct types of nuclei. One nuclear type has the essential gene deleted but has a functional pyrG Allele (pyrG+). The other has the wild-type Allele of the essential gene but lacks a functional pyrG Allele (pyrG−). Thus, a simple growth test applied to the uninucleate asexual spores formed from primary transformants can identify deletions of genes that are non-essential from those that are essential and can only be propagated by heterokaryon rescue. The growth tests also enable the phenotype of the Null Allele to be defined. Diagnostic PCR can be used to confirm deletions at the molecular level. This technique is suitable for large-scale gene-deletion programs and can be completed within 3 weeks. Note: In the version of this article initially published, the black ball in Figure 2c was incorrectly described as representing a pyrG–, geneX+ nuclei. This ball represents pyrG+, geneX–. The error has been corrected in all versions of the article.
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identification and analysis of essential aspergillus nidulans genes using the heterokaryon rescue technique
Nature Protocols, 2006Co-Authors: Aysha H Osmani, Berl R Oakley, Stephen A OsmaniAbstract:In the heterokaryon rescue technique, gene deletions are carried out using the pyrG nutritional marker to replace the coding region of target genes via homologous recombination in Aspergillus nidulans. If an essential gene is deleted, the Null Allele is maintained in spontaneously generated heterokaryons that consist of two genetically distinct types of nuclei. One nuclear type has the essential gene deleted but has a functional pyrG Allele (pyrG+). The other has the wild-type Allele of the essential gene but lacks a functional pyrG Allele (pyrG-). Thus, a simple growth test applied to the uninucleate asexual spores formed from primary transformants can identify deletions of genes that are non-essential from those that are essential and can only be propagated by heterokaryon rescue. The growth tests also enable the phenotype of the Null Allele to be defined. Diagnostic PCR can be used to confirm deletions at the molecular level. This technique is suitable for large-scale gene-deletion programs and can be completed within 3 weeks.
Kathryn N North - One of the best experts on this subject based on the ideXlab platform.
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the effect of heterozygosity for the actn3 Null Allele on human muscle performance
Medicine and Science in Sports and Exercise, 2016Co-Authors: Fleur Garton, Kathryn N NorthAbstract:AB [alpha]-Actinin-3 is primarily expressed in fast (Type II) fibers in the human skeletal muscle. Over 70% of the global population has at least one copy of a loss of function Allele because of a premature stop codon in the ACTN3 gene (R577X). Homozygosity for this variant (577XX) occurs in approximately 16% of humans worldwide and results in complete [alpha]-actinin-3 deficiency, which is detrimental to sprint/power performance and alters adaptation to changing physical demands. The functional implications of [alpha]-actinin-3 deficiency have been the subject of over 90 studies; however, the effect of heterozygosity for the ACTN3 Null Allele is not well documented or understood. Purpose: We reviewed the literature to focus on the most common ACTN3 genotype (577RX) and its effect on human muscle performance. Specifically, we aimed to determine whether the ACTN3 X Allele exerts its effect on human performance only when two copies are present (i.e., in an autosomal recessive fashion). Results: Across a spectrum of conditions, three genotype models (additive, dominant, and recessive) were reported. Most studies assessing healthy adults demonstrated that 577RX heterozygotes performed intermediately (additive model) and/or similarly to the RR genotypes (recessive model). Other studies, (aging, disease/injury, elite sprint performance) showed no definitive genetic model. Conclusions: Assessment of the biological link between dosage, regulation, and function for each ACTN3 genotype is required to improve our understanding of its functional effect and biological penetrance in healthy, aging, and disease populations.
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altered ca2 kinetics associated with α actinin 3 deficiency may explain positive selection for actn3 Null Allele in human evolution
PLOS Genetics, 2015Co-Authors: Stewart I Head, Peter J Houweling, Soren Wagner, Oliver Friedrich, Robyn M. Murphy, Stephen Chan, Kate G R Quinlan, Kathryn N NorthAbstract:Over 1.5 billion people lack the skeletal muscle fast-twitch fibre protein α-actinin-3 due to homozygosity for a common Null polymorphism (R577X) in the ACTN3 gene. α-Actinin-3 deficiency is detrimental to sprint performance in elite athletes and beneficial to endurance activities. In the human genome, it is very difficult to find single-gene loss-of-function variants that bear signatures of positive selection, yet intriguingly, the ACTN3 Null variant has undergone strong positive selection during recent evolution, appearing to provide a survival advantage where food resources are scarce and climate is cold. We have previously demonstrated that α-actinin-3 deficiency in the Actn3 KO mouse results in a shift in fast-twitch fibres towards oxidative metabolism, which would be more “energy efficient” in famine, and beneficial to endurance performance. Prolonged exposure to cold can also induce changes in skeletal muscle similar to those observed with endurance training, and changes in Ca2+ handling by the sarcoplasmic reticulum (SR) are a key factor underlying these adaptations. On this basis, we explored the effects of α-actinin-3 deficiency on Ca2+ kinetics in single flexor digitorum brevis muscle fibres from Actn3 KO mice, using the Ca2+-sensitive dye fura-2. Compared to wild-type, fibres of Actn3 KO mice showed: (i) an increased rate of decay of the twitch transient; (ii) a fourfold increase in the rate of SR Ca2+ leak; (iii) a threefold increase in the rate of SR Ca2+ pumping; and (iv) enhanced maintenance of tetanic Ca2+ during fatigue. The SR Ca2+ pump, SERCA1, and the Ca2+-binding proteins, calsequestrin and sarcalumenin, showed markedly increased expression in muscles of KO mice. Together, these changes in Ca2+ handling in the absence of α-actinin-3 are consistent with cold acclimatisation and thermogenesis, and offer an additional explanation for the positive selection of the ACTN3 577X Null Allele in populations living in cold environments during recent evolution.
Yoshiro Koda - One of the best experts on this subject based on the ideXlab platform.
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two distinct alu mediated deletions of the human abo secretor fut2 locus in samoan and bangladeshi populations
Human Mutation, 2000Co-Authors: Hao Pang, Mikiko Soejima, Yoshiro Koda, Noboru Fujitani, Mohammed Nasimul Islam, A Shamsul K M Islam, Hiroshi KimuraAbstract:The human secretor α(1,2) fucosyltransferase encoded by the FUT2 determines the production of ABO(H) antigens in secretions. Recent studies demonstrated the presence of several nonfunctional Alleles in the FUT2. During the analysis for inactivating mutations at the FUT2 locus from 24 Samoan and 47 Bangladeshi individuals, we found two distinct Alu-mediated deletions of FUT2. The FUT2 deletion in a Bangladeshi population was identical with that found in Indian individuals with the Bombay phenotype (sedel), but not associated with the Null Allele (T725G) of the H gene (FUT1). The FUT2 deletion in Samoans is a novel Null Allele (sedel2). The junction region of sedel2 was successfully amplified using the same primers for the sedel amplification. DNA sequencing of the junction region of the sedel2 indicated that there was a 32-bp sequence identity between DNA sequences surrounding the 5′ and 3′ breakpoints. The size of the deletion of the sedel2 was 9.3 kb, including the full coding region of FUT2. The frequency of the sedel in a Bangladeshi population was 0.074, and that of the sedel2 in a Samoan population was 0.104. Hum Mutat 16:274, 2000. © 2000 Wiley-Liss, Inc.
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ancient origin of the Null Allele se 428 of the human abo secretor locus fut2
Journal of Molecular Evolution, 2000Co-Authors: Yoshiro Koda, Mikiko Soejima, Hidenori Tachida, Osamu Takenaka, Hiroshi KimuraAbstract:In human populations, a Null Allele having several nucleotide differences from the wild-type Allele is segregating at the FUT2 locus (the ABO-Secretor locus) encoding alpha(1,2)fucosyltransferase. To estimate the age of the most recent common ancestor (MRCA) of these two Alleles, we sequenced FUT2 homologues from chimpanzee, gorilla, orangutan, and green monkey. Since we did not detect acceleration or any heterogeneity in the substitution rate at this locus among these species, the age of the MRCA was estimated to be around 3 MYA, assuming the divergence time of human and chimpanzee to be 5 MYA. We developed a simple test to examine whether or not the old age of the MRCA of the FUT2 is consistent with that expected for two divergent neutral Alleles sampled from a random mating population. An application of the test to the data at FUT2 indicated that the age of the MRCA is too old to be explained by the simple neutral assumptions, although our test depends on accurate estimation of the divergence time of human and chimpanzee in units of twice the human population size. Various possibilities including balancing selection are discussed to explain this old age of the MRCA.
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The Fusion Gene at the ABO-Secretor Locus ( FUT2 ): absence in Chinese populations
Journal of Human Genetics, 1999Co-Authors: Yoshiro Koda, Bao-jie Wang, Heung Bum Oh, Mikiko Soejima, Hao Pang, Hiroshi KimuraAbstract:The fusion gene (sefus) is a Null Allele of the secretor type α (1, 2) fucosyltransferase gene (FUT2) and was first found in a Japanese population. It has not yet been reported in any other ethnic population. In the present study, we investigated the distribution of the fusion gene of the FUT2 locus in five populations from three ethnic groups in East Asia. The fusion gene was found in two additional Japanese populations with a high frequency (0.0551 in Okinawa and 0.0792 in Akita) and, for the first time outside Japan, in a Korean population, at a very low frequency (0.0063 in Seoul). In contrast, we found no fusion gene in two Chinese populations. These findings showed that the FUT2 fusion gene was ubiquitous in Japanese, but was rare in neighboring populations, suggesting that the FUT2 fusion gene had emerged from within the Japanese. Additionally, a new Null Allele with a C-to-T substitution at nucleotide 658 was found in one individual native of southern China.
Aysha H Osmani - One of the best experts on this subject based on the ideXlab platform.
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identification and analysis of essential aspergillus nidulans genes using the heterokaryon rescue technique
Nature Protocols, 2006Co-Authors: Aysha H Osmani, Berl R Oakley, Stephen A OsmaniAbstract:In the heterokaryon rescue technique, gene deletions are carried out using the pyrG nutritional marker to replace the coding region of target genes via homologous recombination in Aspergillus nidulans. If an essential gene is deleted, the Null Allele is maintained in spontaneously generated heterokaryons that consist of two genetically distinct types of nuclei. One nuclear type has the essential gene deleted but has a functional pyrG Allele (pyrG+). The other has the wild-type Allele of the essential gene but lacks a functional pyrG Allele (pyrG−). Thus, a simple growth test applied to the uninucleate asexual spores formed from primary transformants can identify deletions of genes that are non-essential from those that are essential and can only be propagated by heterokaryon rescue. The growth tests also enable the phenotype of the Null Allele to be defined. Diagnostic PCR can be used to confirm deletions at the molecular level. This technique is suitable for large-scale gene-deletion programs and can be completed within 3 weeks. Note: In the version of this article initially published, the black ball in Figure 2c was incorrectly described as representing a pyrG–, geneX+ nuclei. This ball represents pyrG+, geneX–. The error has been corrected in all versions of the article.
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identification and analysis of essential aspergillus nidulans genes using the heterokaryon rescue technique
Nature Protocols, 2006Co-Authors: Aysha H Osmani, Berl R Oakley, Stephen A OsmaniAbstract:In the heterokaryon rescue technique, gene deletions are carried out using the pyrG nutritional marker to replace the coding region of target genes via homologous recombination in Aspergillus nidulans. If an essential gene is deleted, the Null Allele is maintained in spontaneously generated heterokaryons that consist of two genetically distinct types of nuclei. One nuclear type has the essential gene deleted but has a functional pyrG Allele (pyrG+). The other has the wild-type Allele of the essential gene but lacks a functional pyrG Allele (pyrG-). Thus, a simple growth test applied to the uninucleate asexual spores formed from primary transformants can identify deletions of genes that are non-essential from those that are essential and can only be propagated by heterokaryon rescue. The growth tests also enable the phenotype of the Null Allele to be defined. Diagnostic PCR can be used to confirm deletions at the molecular level. This technique is suitable for large-scale gene-deletion programs and can be completed within 3 weeks.
