Whole-Genome SNP Association in the Horse: Identification of a Deletion in Myosin Va Responsible for Lavender Foal Syndrome
Lavender Foal Syndrome (LFS) is a lethal inherited disease of horses with a suspected autosomal recessive mode of inheritance. LFS has been primarily diagnosed in a subgroup of the Arabian breed, the Egyptian Arabian horse. The condition is characterized by multiple neurological abnormalities and a dilute coat color. Candidate genes based on comparative phenotypes in mice and humans include the ras-associated protein RAB27a (RAB27A) and myosin Va (MYO5A). Here we report mapping of the locus responsible for LFS using a small set of 36 horses segregating for LFS. These horses were genotyped using a newly available single nucleotide polymorphism (SNP) chip containing 56,402 discriminatory elements. The whole genome scan identified an associated region containing these two functional candidate genes. Exon sequencing of the MYO5A gene from an affected foal revealed a single base deletion in exon 30 that changes the reading frame and introduces a premature stop codon. A PCR–based Restriction Fragment Length Polymorphism (PCR–RFLP) assay was designed and used to investigate the frequency of the mutant gene. All affected horses tested were homozygous for this mutation. Heterozygous carriers were detected in high frequency in families segregating for this trait, and the frequency of carriers in unrelated Egyptian Arabians was 10.3%. The mapping and discovery of the LFS mutation represents the first successful use of whole-genome SNP scanning in the horse for any trait. The RFLP assay can be used to assist breeders in avoiding carrier-to-carrier matings and thus in preventing the birth of affected foals.
Vyšlo v časopise:
Whole-Genome SNP Association in the Horse: Identification of a Deletion in Myosin Va Responsible for Lavender Foal Syndrome. PLoS Genet 6(4): e32767. doi:10.1371/journal.pgen.1000909
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1000909
Souhrn
Lavender Foal Syndrome (LFS) is a lethal inherited disease of horses with a suspected autosomal recessive mode of inheritance. LFS has been primarily diagnosed in a subgroup of the Arabian breed, the Egyptian Arabian horse. The condition is characterized by multiple neurological abnormalities and a dilute coat color. Candidate genes based on comparative phenotypes in mice and humans include the ras-associated protein RAB27a (RAB27A) and myosin Va (MYO5A). Here we report mapping of the locus responsible for LFS using a small set of 36 horses segregating for LFS. These horses were genotyped using a newly available single nucleotide polymorphism (SNP) chip containing 56,402 discriminatory elements. The whole genome scan identified an associated region containing these two functional candidate genes. Exon sequencing of the MYO5A gene from an affected foal revealed a single base deletion in exon 30 that changes the reading frame and introduces a premature stop codon. A PCR–based Restriction Fragment Length Polymorphism (PCR–RFLP) assay was designed and used to investigate the frequency of the mutant gene. All affected horses tested were homozygous for this mutation. Heterozygous carriers were detected in high frequency in families segregating for this trait, and the frequency of carriers in unrelated Egyptian Arabians was 10.3%. The mapping and discovery of the LFS mutation represents the first successful use of whole-genome SNP scanning in the horse for any trait. The RFLP assay can be used to assist breeders in avoiding carrier-to-carrier matings and thus in preventing the birth of affected foals.
Zdroje
1. BowlingAT
1996 Medical Genetics. Horse Genetics Wallingford, UK CABI International 105 106
2. FanelliHH
2005 Coat colour dilution lethal (‘lavender foal syndrome’): a tetany syndrome of Arabian foals. Equine Veterinary Education 17 260 263
3. PageP
ParkerR
HarperC
GuthrieA
NeserJ
2006 Clinical, clinicopathologic, postmortem examination findings and familial history of 3 Arabians with lavender foal syndrome. J Vet Intern Med 20 1491 1494
4. Arabian Horse Association 2009 Arabian Horse History & Heritage
5. GuerinG
BaileyE
BernocoD
AndersonI
AntczakDF
1999 Report of the International Equine Gene Mapping Workshop: male linkage map. Anim Genet 30 341 354
6. PenedoMC
MillonLV
BernocoD
BaileyE
BinnsM
2005 International Equine Gene Mapping Workshop Report: a comprehensive linkage map constructed with data from new markers and by merging four mapping resources. Cytogenet Genome Res 111 5 15
7. ValbergSJ
WardTL
RushB
KindeH
HiraragiH
2001 Glycogen branching enzyme deficiency in quarter horse foals. J Vet Intern Med 15 572 580
8. TryonRC
WhiteSD
BannaschDL
2007 Homozygosity mapping approach identifies a missense mutation in equine cyclophilin B (PPIB) associated with HERDA in the American Quarter Horse. Genomics 90 93 102
9. WadeCM
GiulottoE
SigurdssonS
ZoliM
GnerreS
2009 Genome sequence, comparative analysis, and population genetics of the domestic horse. Science 326 865 867
10. KarlssonEK
BaranowskaI
WadeCM
Salmon HillbertzNH
ZodyMC
2007 Efficient mapping of mendelian traits in dogs through genome-wide association. Nat Genet 39 1321 1328
11. CharlierC
CoppietersW
RollinF
DesmechtD
AgerholmJS
2008 Highly effective SNP-based association mapping and management of recessive defects in livestock. Nat Genet 40 449 454
12. MarksMS
SeabraMC
2001 The melanosome: membrane dynamics in black and white. Nat Rev Mol Cell Biol 2 738 748
13. BramhamCR
WellsDG
2007 Dendritic mRNA: transport, translation and function. Nat Rev Neurosci 8 776 789
14. GodaY
2008 Neuroscience: Along memory lane. Nature 456 590 591
15. BultCJ
EppigJT
KadinJA
RichardsonJE
BlakeJA
2008 The Mouse Genome Database (MGD): mouse biology and model systems. Nucleic Acids Res 36 D724 728
16. SanalO
ErsoyF
TezcanI
MetinA
YelL
2002 Griscelli disease: genotype-phenotype correlation in an array of clinical heterogeneity. J Clin Immunol 22 237 243
17. Van GeleM
DynoodtP
LambertJ
2009 Griscelli syndrome: a model system to study vesicular trafficking. Pigment Cell Melanoma Res 22 268 282
18. PashkovaN
CatlettNL
NovakJL
WuG
LuR
2005 Myosin V attachment to cargo requires the tight association of two functional subdomains. J Cell Biol 168 359 364
19. AuJS
HuangJD
2002 A tissue-specific exon of myosin Va is responsible for selective cargo binding in melanocytes. Cell Motil Cytoskeleton 53 89 102
20. HuangJD
MermallV
StrobelMC
RussellLB
MoosekerMS
1998 Molecular genetic dissection of mouse unconventional myosin-VA: tail region mutations. Genetics 148 1963 1972
21. TryonRC
PenedoMC
McCueME
ValbergSJ
MickelsonJR
2009 Evaluation of allele frequencies of inherited disease genes in subgroups of American Quarter Horses. J Am Vet Med Assoc 234 120 125
22. BernocoD
BaileyE
1998 Frequency of the SCID gene among Arabian horses in the USA. Anim Genet 29 41 42
23. LockeMM
PenedoMC
BrickerSJ
MillonLV
MurrayJD
2002 Linkage of the grey coat colour locus to microsatellites on horse chromosome 25. Anim Genet 33 329 337
24. PurcellS
NealeB
Todd-BrownK
ThomasL
FerreiraMA
2007 PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81 559 575
25. R Development Core Team 2008 R: A language and environment for statistical computing. Vienna, Austria R foundation for Statistical Computing
26. BarrettJC
FryB
MallerJ
DalyMJ
2005 Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21 263 265
27. StephensM
SmithNJ
DonnellyP
2001 A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 68 978 989
28. KuhnRM
KarolchikD
ZweigAS
WangT
SmithKE
2009 The UCSC Genome Browser Database: update 2009. Nucleic Acids Res 37 D755 761
29. UntergasserA
NijveenH
RaoX
BisselingT
GeurtsR
2007 Primer3Plus, an enhanced web interface to Primer3. Nucleic Acids Res 35 W71 74
30. LarkinMA
BlackshieldsG
BrownNP
ChennaR
McGettiganPA
2007 Clustal W and Clustal X version 2.0. Bioinformatics 23 2947 2948
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
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