Identification of a doublet missense substitution in the bovine LRP4 gene as a candidate causal mutation for syndactyly in Holstein cattle

Duchesne, Amandine; Gautier, Mathieu; Chadi, Sead; Grohs, Cécile; Floriot, Sandrine; Gallard, Yves; Caste, G.; Ducos, Alain; Eggen, Andre A.

doi:10.1016/j.ygeno.2006.05.007

Cited by 47 publications

(42 citation statements)

References 34 publications

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“…Pedigree information was available for 4 breeds: HOL, NOR, MON, and CHA. Of the 1022 HOL individuals, 973 are AI bulls organized in 17 half-sib families (30-117 individuals/ family) and 49 belong to a complex pedigree in which the causal polymorphism for syndactyly segregates (Duchesne et al 2006). For NOR and MON, the samples consist of 275 and 197 AI bulls, respectively, organized in six and four half-sib families (18-66 and 10-65 bulls/family).…”

Section: Methodsmentioning

confidence: 99%

“…For the remaining four breeds (CHA, HOL, MON, and NOR), we selected only a small subset of individuals from the available pedigrees: i.e., for the CHA breed, 25 founder individuals (with no parental information), and for the HOL, MON, and NOR breeds, two to four individuals/half-sib family without any common ancestor for at least three generations on the maternal side. For HOL, 6 founder individuals from the pedigree segregating the syndactyly causal mutation (Duchesne et al 2006) were also included in the sample. Finally, 39, 36, and 33 individuals were selected for the HOL, MON, and NOR breeds, respectively.…”

Section: Methodsmentioning

confidence: 99%

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Genetic and Haplotypic Structure in 14 European and African Cattle Breeds

et al. 2007

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To evaluate and compare the extent of LD in cattle, 1536 SNPs, mostly localized on BTA03, were detected in silico from available sequence data using two different methods and genotyped on samples from 14 distinct breeds originating from Europe and Africa. Only 696 SNPs could be validated, confirming the importance of trace-quality information for the in silico detection. Most of the validated SNPs were informative in several breeds and were used for a detailed description of their genetic structure and relationships. Results obtained were in agreement with previous studies performed on microsatellite markers and using larger samples. In addition, the majority of the validated SNPs could be mapped precisely, reaching an average density of one marker every 311 kb. This allowed us to analyze the extent of LD in the different breeds. Decrease of LD with physical distance across breeds revealed footprints of ancestral LD at short distances (,10 kb). As suggested by the haplotype block structure, these ancestral blocks are organized, within a breed, into larger blocks of a few hundred kilobases. In practice, such a structure similar to that already reported in dogs makes it possible to develop a chip of ,300,000 SNPs, which should be efficient for mapping purposes in most cattle breeds.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Genetic and Haplotypic Structure in 14 European and African Cattle Breeds

et al. 2007

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“…Several distinct strains of LRP4 mutant mice have been generated by gene targeting (42,43). LRP4 loss-of-function mutations have also spontaneously and independently arisen in several viable mouse and cattle strains (43)(44)(45)(46)(47). In each of these cases, polysyndactyly, i.e.…”

Section: Lrp4mentioning

confidence: 99%

Expanding functions of lipoprotein receptors

Herz

Chen

Masiulis

et al. 2009

Journal of Lipid Research

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Lipoprotein receptors are evolutionarily ancient proteins that are expressed on the surface of many cell types. Beginning with the appearance of the first primitive multicellular organisms, several structurally and functionally distinct families of lipoprotein receptors evolved. Originally, these cell surface proteins were thought to merely mediate the traffic of lipids and nutrients between cells and, in some cases, by functioning as scavenger receptors, remove other kinds of macromolecules, such as proteases and protease inhibitors from the extracellular space and the cell surface. Over the last decade, this picture has fundamentally changed. We now appreciate that many of these receptors are not mere cargo transporters; they are deeply embedded in the machinery by which cells communicate with each other. By physically interacting and coevolving with fundamental signaling pathways, lipoprotein receptors have occupied essential and surprisingly diverse functions that are indispensable for integrating the complex web of cellular signal input during development and in differentiated tissues. Lipid transport through the circulation, the extracellular space, and across the plasma membrane involves the concerted action of a wide range of cell surface receptors, lipid carrier and transfer proteins, enzymes, and cellular transporters. As an evolutionarily ancient process, it probably arose to distribute essential nutritional or endogenously synthesized lipids and hormones but also lipid modified signaling proteins and other associated macromolecules between increasingly metabolically specialized tissues. Lipoprotein receptors are among the oldest components of this complex biochemical system. These cell surface receptors fall into two major groups: endocytic receptors that bind their cargo in the form of lipid carrying lipoproteins and mediate their internalization and eventually lysosomal delivery, and a second group that promotes lipid exchange at the plasma membrane without cellular uptake of the protein component of the particle. In addition to their specialized functions as mediators of cellular lipid uptake, lipoprotein receptors have, over the last few years, also been recognized for often unrelated roles as cellular signal transducers or signal modulators. In this review, we will restrict ourselves to only one particularly versatile subgroup of these receptors, the LDL receptor gene family (Fig. 1), and its expanding functions in the nervous system. ROLES OF THE LDL RECEPTOR GENE FAMILY IN THE NERVOUS SYSTEMSeveral members of the LDL receptor gene family are involved in a wide range of signaling pathways that control fundamental developmental processes in the embryo, as well as tissue remodeling in the adult organism. Here, the expanding roles of the gene family in the nervous system deserve particular attention. First, a stream of evidence is emerging that several members of the family are directly or indirectly involved in neuronal survival and degeneration, specifically in the incompletely understo...

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“…First, our results document that LRP4 was expressed by CLL cells in virtually all cases when tested by multiple assays. Second, LRP4 rs2306029 is a non-synonymous SNP leading to amino acid substitution at position 1554 within an evolutionarily conserved site of the LRP4 LDL-receptor class B beta-propeller motif, that is necessary for proper folding, stability and functioning of the LRP4 protein (Tomita et al, 1998;Duchesne et al, 2006;Simon-Chazottes et al, 2006;Drögemüller et al, 2007;Dietrich et al, 2010;Li et al, 2010). Third, bioinformatic analysis performed in this study scores LRP4 rs2306029 as a variant with possible deleterious and damaging effects on LRP4 protein function.…”

Section: Discussionmentioning

confidence: 82%

A variant of the LRP4 gene affects the risk of chronic lymphocytic leukaemia transformation to Richter syndrome

et al. 2010

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SummaryRichter syndrome (RS) represents the transformation of chronic lymphocytic leukaemia (CLL) to aggressive lymphoma. Risk factors of CLL transformation to RS are only partly known. We explored the role of the host genetic background as a risk factor for RS occurrence. Forty‐five single nucleotide polimorphisms (SNPs) known to be relevant for CLL prognosis were genotyped in a consecutive cohort of 331 CLL, of which 21 had transformed to RS. After correcting for multiple testing and adjusting for previously reported RS risk factors, the LRP4 rs2306029 TT variant genotype was the sole SNP independently associated with a higher risk of RS transformation (Hazard Ratio: 4·17; P = 0·001; q = 0·047). The enrichment of LRP4 TT genotype in RS was confirmed in an independent series (n = 44) used for validation purposes. The LRP4 protein was expressed in CLL (n = 66). Bioinformatic analysis scored LRP4 rs2306029 as a variant with possible deleterious and damaging variant of LRP4. LRP4 genotyping may help the recognition of patients with increased risk of RS at the time of CLL diagnosis.

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Identification of a doublet missense substitution in the bovine LRP4 gene as a candidate causal mutation for syndactyly in Holstein cattle

Cited by 47 publications

References 34 publications

Genetic and Haplotypic Structure in 14 European and African Cattle Breeds

Genetic and Haplotypic Structure in 14 European and African Cattle Breeds

Expanding functions of lipoprotein receptors

A variant of the LRP4 gene affects the risk of chronic lymphocytic leukaemia transformation to Richter syndrome

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