Systematic genome-wide approach to positional candidate cloning for identification of novel human disease genes

2004 ◽  
Vol 34 (3) ◽  
pp. 79-90 ◽  
Author(s):  
H. Kiyosawa ◽  
T. Kawashima ◽  
D. Silva ◽  
N. Petrovsky ◽  
Y. Hasegawa ◽  
...  
Keyword(s):  
Human Disease ◽  
Disease Genes ◽  
Positional Candidate ◽  
Genome Wide ◽  
Human Disease Genes ◽  
Positional Candidate Cloning

scholarly journals Identification of Quantitative Trait Loci for Production Traits in Commercial Pig Populations

Genetics ◽  
2003 ◽  
Vol 164 (2) ◽  
pp. 621-627 ◽  
Author(s):  
G J Evans ◽  
E Giuffra ◽  
A Sanchez ◽  
S Kerje ◽  
G Davalos ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Marker Assisted Selection ◽  
Selection Pressure ◽  
Phenotypic Variance ◽  
Quality Traits ◽  
Production Traits ◽  
Positional Candidate ◽  
Different Populations ◽  
Positional Candidate Cloning ◽  
Selection Of

Abstract The aim of this study was to investigate methods for detecting QTL in outbred commercial pig populations. Several QTL for back fat and growth rate, previously detected in experimental resource populations, were examined for segregation in 10 different populations. Two hundred trait-by-population-by-chromosome tests were performed, resulting in 20 tests being significant at the 5% level. In addition, 53 QTL tests for 11 meat quality traits were declared significant, using a subset of the populations. These results show that a considerable amount of phenotypic variance observed in these populations can be explained by major alleles segregating at several of the loci described. Thus, despite a relatively strong selection pressure for growth and back fat traits in these populations, these alleles have not yet reached fixation. The approaches used here demonstrate that it is possible to verify segregation of QTL in commercial populations by limited genotyping of a selection of informative animals. Such verified QTL may be directly exploited in marker-assisted selection (MAS) programs in commercial populations and their molecular basis may be revealed by positional candidate cloning.

Analysis of the sheep genome

2001 ◽  
Vol 7 (2) ◽  
pp. 69-78 ◽  
Author(s):  
N. E. COCKETT ◽  
T. L. SHAY ◽  
M. SMIT
Keyword(s):  
Genetic Variability ◽  
Genetic Analysis ◽  
Chromosomal Region ◽  
Mammalian Species ◽  
Biological Pathways ◽  
Polymorphic Markers ◽  
Positional Candidate ◽  
Naturally Occurring ◽  
Comparative Maps ◽  
Positional Candidate Cloning

The identification of genes controlling several traits of interest in sheep has been accomplished by positional candidate cloning. In these studies, the trait is first mapped to a specific chromosomal region by linkage analysis, which requires families that are segregating for the trait and for polymorphic markers. Microsatellite markers are usually used for these analyses because of their extensive genetic variability. Once the location of a trait is determined by linkage to the markers, possible candidate genes controlling the trait can be inferred because of their proximity to linked markers. It is not necessary to map all possible genes in sheep for this strategy to be effective. Rather, a subset of genes that are mapped in humans and mice have also been mapped in sheep; these genes serve as “anchors” across the comparative maps of the different species. Further study of these positional candidates has revealed naturally occurring mutations that produce phenotypes that are unique to sheep. Thus the genetic analysis of sheep traits advances knowledge not only in this species but provides critical information for understanding biological pathways in mammalian species.

scholarly journals A Nonsense Variant in Hephaestin Like 1 (HEPHL1) Is Responsible for Congenital Hypotrichosis in Belted Galloway Cattle

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 643
Author(s):  
Thibaud Kuca ◽  
Brandy M. Marron ◽  
Joana G. P. Jacinto ◽  
Julia M. Paris ◽  
Christian Gerspach ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Homozygosity Mapping ◽  
Mendelian Inheritance ◽  
Large Animal Model ◽  
Large Animal ◽  
Loss Of Function ◽  
Protein Coding ◽  
Positional Candidate ◽  
Genome Wide ◽  
A Genome

Genodermatosis such as hair disorders mostly follow a monogenic mode of inheritance. Congenital hypotrichosis (HY) belong to this group of disorders and is characterized by abnormally reduced hair since birth. The purpose of this study was to characterize the clinical phenotype of a breed-specific non-syndromic form of HY in Belted Galloway cattle and to identify the causative genetic variant for this recessive disorder. An affected calf born in Switzerland presented with multiple small to large areas of alopecia on the limbs and on the dorsal part of the head, neck, and back. A genome-wide association study using Swiss and US Belted Galloway cattle encompassing 12 cases and 61 controls revealed an association signal on chromosome 29. Homozygosity mapping in a subset of cases refined the HY locus to a 1.5 Mb critical interval and subsequent Sanger sequencing of protein-coding exons of positional candidate genes revealed a stop gain variant in the HEPHL1 gene that encodes a multi-copper ferroxidase protein so-called hephaestin like 1 (c.1684A>T; p.Lys562*). A perfect concordance between the homozygous presence of this most likely pathogenic loss-of-function variant and the HY phenotype was found. Genotyping of more than 700 purebred Swiss and US Belted Galloway cattle showed the global spread of the mutation. This study provides a molecular test that will permit the avoidance of risk matings by systematic genotyping of relevant breeding animals. This rare recessive HEPHL1-related form of hypotrichosis provides a novel large animal model for similar human conditions. The results have been incorporated in the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 002230-9913).

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