Benoît Brouwers - Academia.edu (original) (raw)

Papers by Benoît Brouwers

Research paper thumbnail of A deletion in the bovine myostatin gene causes the double–muscled phenotype in cattle

Research paper thumbnail of An imprinted QTL with major effect on muscle mass and fat deposition maps to the IGF2 locus in pigs

Nature Genetics, 1999

Jump to main content; Jump to navigation; nature.com homepage; Publications AZ index; Browse by s... more Jump to main content; Jump to navigation; nature.com homepage; Publications AZ index; Browse by subject. My account; Submit Manuscript; Register; Subscribe. Login. Search Advanced search. Error: page not found. You might ...

Research paper thumbnail of A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle

Research paper thumbnail of Haplotype sharing refines the location of an imprinted quantitative trait locus with major effect on muscle mass to a 250-kb chromosome segment containing the porcine IGF2 gene

Genetics, 2003

We herein describe the fine mapping of an imprinted QTL with major effect on muscle mass that was... more We herein describe the fine mapping of an imprinted QTL with major effect on muscle mass that was previously assigned to distal SSC2p in the pig. The proposed approach exploits linkage disequilibrium in combination with QTL genotyping by marker-assisted segregation analysis. By identifying a haplotype shared by all "Q" chromosomes, we map the QTL to an approximately 250-kb chromosome segment containing INS and IGF2 as the only known paternally expressed genes. This considerably reinforces the candidacy of these genes, justifying their detailed analysis.

Research paper thumbnail of Clinicopathological Features of Inflammatory versus Noninflammatory Locally Advanced Nonmetastatic Breast Cancer

Tumor Biology, 2008

Background: Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer. It i... more Background: Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer. It is mainly a clinical diagnosis. The aim of this study was to compare IBC to clinically diagnosed noninflammatory locally advanced nonmetastatic breast cancer, also called cLABC. Material and Methods: One hundred and eight patients were studied: 49 with IBC and 59 with cLABC. The following

Research paper thumbnail of High-resolution, human–bovine comparative mapping based on a closed YAC contig spanning the bovine mh locus

Mammalian Genome, 1999

A closed YAC contig spanning the mh locus was assembled by STS content mapping with seven microsa... more A closed YAC contig spanning the mh locus was assembled by STS content mapping with seven microsatellite markers, eight genes or EST, and nine STS corresponding to YAC ends. The contig comprises 27 YACs, has an average depth of 4.3 YACs, and spans an estimated 1.2 Mb. A linkage map was constructed based on five of the microsatellite markers anchored to the contig and shown to span 7 cM, yielding a ratio of 160 kb/1 cM for the corresponding chromosome region. Comparative mapping data indicate that the constructed contig spans an evolutionary breakpoint connecting two chromosome segments that are syntenic but not adjacent in the human. Consolidation of human gene order by means of whole genome radiation hybrids and its comparison with the bovine order as inferred from the contig confirm conservation of gene order within segments.

Research paper thumbnail of Towards interbreed IBD fine mapping of the mh locus: Double-muscling in the Asturiana de los Valles breed involves the same locus as in the Belgian Blue cattle breed

Mammalian Genome, 1997

The Spanish "Asturiana" cattle breed is characterized by the segregation of a g... more The Spanish "Asturiana" cattle breed is characterized by the segregation of a genetically determined muscular hypertrophy referred to as double-muscling or "culones". We demonstrate by linkage analysis that this muscular hypertrophy involves the mh locus previously shown to cause double-muscling in the Belgian Blue cattle breed, pointing towards locus homogeneity of this trait across both breeds. Moreover, using a twopoint and multipoint maximum likelihood approach, we show that flanking microsatellite markers are in linkage disequilibrium with the mh locus in both breeds albeit with different alleles. Finally, we discuss how allelic homogeneity across breeds might be exploited to achieve efficient genetic fine-mapping of the mh locus.

Research paper thumbnail of Identity-by-descent mapping of recessive traits in livestock: application to map the bovine syndactyly locus to chromosome 15

Genome Research, 1996

Twelve animals affected with syndactyly or mulefoot were sampled in the Dutch black-and-white cat... more Twelve animals affected with syndactyly or mulefoot were sampled in the Dutch black-and-white cattle population. Analysis of the pedigree data reveal that all of these individuals traced back to a single acknowledged carrier founder individual. Between seven and nine generations separated the founder from its 12 affected descendents. The 12 affected offspring were genotyped for a battery of 213 microsatellites spanning the 29 bovine autosomes. The resulting genotypes were analyzed using a maximum likelihood approach searching for shared homozygous haplotypes among affected individuals. Three candidate regions for the syndactyly locus emerged from this initial screening. syndactyly was shown to map to one of these candidate regions on chromosome 15 by genotyping 29 additional individuals linking founder and affected offspring and performing a conventional linkage analysis with the LINKAGE programs. This study illustrates the potential of identity-by-descent mapping in livestock populations.

Research paper thumbnail of Modulating skeletal muscle mass by postnatal, muscle-specific inactivation of the myostatin gene

genesis, 2003

By using a conditional gene targeting approach exploiting the cre-lox system, we show that postna... more By using a conditional gene targeting approach exploiting the cre-lox system, we show that postnatal inactivation of the myostatin gene in striated muscle is sufficient to cause a generalized muscular hypertrophy of the same magnitude as that observed for constitutive myostatin knockout mice. This formally demonstrates that striated muscle is the production site of functional myostatin and that this member of the TGF␤ family of growth and differentiation factors regulates muscle mass not only during early embryogenesis but throughout development. It indicates that myostatin antagonist could be used to treat muscle wasting and to promote muscle growth in man and animals. genesis 35:227-238, 2003.

Research paper thumbnail of Molecular definition of an allelic series of mutations disrupting the myostatin function and causing double-muscling in cattle

Mammalian Genome, 1998

We have determined the entire myostatin coding sequence for 32 double-muscled cattle sampled from... more We have determined the entire myostatin coding sequence for 32 double-muscled cattle sampled from ten European cattle breeds. Seven DNA sequence polymorphisms were identified, of which five would be predicted to disrupt the function of the protein, one is a conservative amino acid substitution, and one a silent DNA sequence variant. Four additional DNA sequence polymorphisms were identified in myostatin intronic sequences. In all but two breeds, all double-muscled animals were either homozygous or compound heterozygotes for one of the five loss-offunction mutations. The absence of obvious loss-of-function mutations in the coding sequence of the two remaining breeds points either towards additional mutations in unexplored segments of the gene, or towards locus heterogeneity of double-muscling.

Research paper thumbnail of A deletion in the bovine myostatin gene causes the double–muscled phenotype in cattle

Research paper thumbnail of An imprinted QTL with major effect on muscle mass and fat deposition maps to the IGF2 locus in pigs

Nature Genetics, 1999

Jump to main content; Jump to navigation; nature.com homepage; Publications AZ index; Browse by s... more Jump to main content; Jump to navigation; nature.com homepage; Publications AZ index; Browse by subject. My account; Submit Manuscript; Register; Subscribe. Login. Search Advanced search. Error: page not found. You might ...

Research paper thumbnail of A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle

Research paper thumbnail of Haplotype sharing refines the location of an imprinted quantitative trait locus with major effect on muscle mass to a 250-kb chromosome segment containing the porcine IGF2 gene

Genetics, 2003

We herein describe the fine mapping of an imprinted QTL with major effect on muscle mass that was... more We herein describe the fine mapping of an imprinted QTL with major effect on muscle mass that was previously assigned to distal SSC2p in the pig. The proposed approach exploits linkage disequilibrium in combination with QTL genotyping by marker-assisted segregation analysis. By identifying a haplotype shared by all "Q" chromosomes, we map the QTL to an approximately 250-kb chromosome segment containing INS and IGF2 as the only known paternally expressed genes. This considerably reinforces the candidacy of these genes, justifying their detailed analysis.

Research paper thumbnail of Clinicopathological Features of Inflammatory versus Noninflammatory Locally Advanced Nonmetastatic Breast Cancer

Tumor Biology, 2008

Background: Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer. It i... more Background: Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer. It is mainly a clinical diagnosis. The aim of this study was to compare IBC to clinically diagnosed noninflammatory locally advanced nonmetastatic breast cancer, also called cLABC. Material and Methods: One hundred and eight patients were studied: 49 with IBC and 59 with cLABC. The following

Research paper thumbnail of High-resolution, human–bovine comparative mapping based on a closed YAC contig spanning the bovine mh locus

Mammalian Genome, 1999

A closed YAC contig spanning the mh locus was assembled by STS content mapping with seven microsa... more A closed YAC contig spanning the mh locus was assembled by STS content mapping with seven microsatellite markers, eight genes or EST, and nine STS corresponding to YAC ends. The contig comprises 27 YACs, has an average depth of 4.3 YACs, and spans an estimated 1.2 Mb. A linkage map was constructed based on five of the microsatellite markers anchored to the contig and shown to span 7 cM, yielding a ratio of 160 kb/1 cM for the corresponding chromosome region. Comparative mapping data indicate that the constructed contig spans an evolutionary breakpoint connecting two chromosome segments that are syntenic but not adjacent in the human. Consolidation of human gene order by means of whole genome radiation hybrids and its comparison with the bovine order as inferred from the contig confirm conservation of gene order within segments.

Research paper thumbnail of Towards interbreed IBD fine mapping of the mh locus: Double-muscling in the Asturiana de los Valles breed involves the same locus as in the Belgian Blue cattle breed

Mammalian Genome, 1997

The Spanish "Asturiana" cattle breed is characterized by the segregation of a g... more The Spanish "Asturiana" cattle breed is characterized by the segregation of a genetically determined muscular hypertrophy referred to as double-muscling or "culones". We demonstrate by linkage analysis that this muscular hypertrophy involves the mh locus previously shown to cause double-muscling in the Belgian Blue cattle breed, pointing towards locus homogeneity of this trait across both breeds. Moreover, using a twopoint and multipoint maximum likelihood approach, we show that flanking microsatellite markers are in linkage disequilibrium with the mh locus in both breeds albeit with different alleles. Finally, we discuss how allelic homogeneity across breeds might be exploited to achieve efficient genetic fine-mapping of the mh locus.

Research paper thumbnail of Identity-by-descent mapping of recessive traits in livestock: application to map the bovine syndactyly locus to chromosome 15

Genome Research, 1996

Twelve animals affected with syndactyly or mulefoot were sampled in the Dutch black-and-white cat... more Twelve animals affected with syndactyly or mulefoot were sampled in the Dutch black-and-white cattle population. Analysis of the pedigree data reveal that all of these individuals traced back to a single acknowledged carrier founder individual. Between seven and nine generations separated the founder from its 12 affected descendents. The 12 affected offspring were genotyped for a battery of 213 microsatellites spanning the 29 bovine autosomes. The resulting genotypes were analyzed using a maximum likelihood approach searching for shared homozygous haplotypes among affected individuals. Three candidate regions for the syndactyly locus emerged from this initial screening. syndactyly was shown to map to one of these candidate regions on chromosome 15 by genotyping 29 additional individuals linking founder and affected offspring and performing a conventional linkage analysis with the LINKAGE programs. This study illustrates the potential of identity-by-descent mapping in livestock populations.

Research paper thumbnail of Modulating skeletal muscle mass by postnatal, muscle-specific inactivation of the myostatin gene

genesis, 2003

By using a conditional gene targeting approach exploiting the cre-lox system, we show that postna... more By using a conditional gene targeting approach exploiting the cre-lox system, we show that postnatal inactivation of the myostatin gene in striated muscle is sufficient to cause a generalized muscular hypertrophy of the same magnitude as that observed for constitutive myostatin knockout mice. This formally demonstrates that striated muscle is the production site of functional myostatin and that this member of the TGF␤ family of growth and differentiation factors regulates muscle mass not only during early embryogenesis but throughout development. It indicates that myostatin antagonist could be used to treat muscle wasting and to promote muscle growth in man and animals. genesis 35:227-238, 2003.

Research paper thumbnail of Molecular definition of an allelic series of mutations disrupting the myostatin function and causing double-muscling in cattle

Mammalian Genome, 1998

We have determined the entire myostatin coding sequence for 32 double-muscled cattle sampled from... more We have determined the entire myostatin coding sequence for 32 double-muscled cattle sampled from ten European cattle breeds. Seven DNA sequence polymorphisms were identified, of which five would be predicted to disrupt the function of the protein, one is a conservative amino acid substitution, and one a silent DNA sequence variant. Four additional DNA sequence polymorphisms were identified in myostatin intronic sequences. In all but two breeds, all double-muscled animals were either homozygous or compound heterozygotes for one of the five loss-offunction mutations. The absence of obvious loss-of-function mutations in the coding sequence of the two remaining breeds points either towards additional mutations in unexplored segments of the gene, or towards locus heterogeneity of double-muscling.