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Topic:Genetics

Genetics in horses encompasses the study of hereditary traits and the genetic makeup that influences various characteristics and health conditions in equine populations. This field involves the analysis of genes and their functions, inheritance patterns, and the impact of genetic variations on traits such as coat color, performance ability, and susceptibility to diseases. Research in equine genetics employs techniques such as genome mapping, sequencing, and genetic testing to identify specific genes and mutations associated with these traits. This page gathers peer-reviewed research studies and scholarly articles that explore the genetic basis of equine traits, the methodologies used in genetic research, and the implications for breeding, health management, and conservation of horse breeds.
Long terminal repeats are not the sole determinants of virulence for equine infectious anemia virus.
Archives of virology    August 24, 2006   Volume 152, Issue 1 209-218 doi: 10.1007/s00705-006-0830-z
Tu YB, Zhou T, Yuan XF, Qiu HJ, Xue F, Sun CQ, Wang L, Wu DL, Peng JM, Kong XG, Tong GZ.The long terminal repeats (LTRs) of equine infectious anemia virus donkey leukocyte-attenuated virus (EIAV-DLA) were substituted with those of the wild-type EIAV-L (wt EIAV-L, the parent virus of EIAV-DLA). The resulting chimeric plasmid was designated pOK-LTR DLA/L. Purified pOK-LTR DLA/L was transfected into monocyte-derived macrophage (MDM) cultures prepared from EIAV-negative, heparinized whole blood from a donkey. Eighth-passage cell cultures developed the typical cytopathogenic effects (CPE) of EIAV infection, and virions with typical EIAV profiles were observed with an electron microsco...
Reverse transcriptase-polymerase chain reaction for the detection equine rhinitis B viruses and cell culture isolation of the virus.
Archives of virology    August 24, 2006   Volume 152, Issue 1 137-149 doi: 10.1007/s00705-006-0810-3
Black WD, Hartley CA, Ficorilli NP, Studdert MJ.Equine rhinitis B virus (ERBV), genus Erbovirus, family Picornaviridae occurs as two serotypes, ERBV1 and ERBV2. An ERBV-specific nested reverse transcriptase-polymerase chain reaction (RT-PCR) that amplified a product within the 3D(pol) and 3' non-translated region of the viral genome was developed. The RT-PCR detected all 24 available ERBV1 isolates and one available ERBV2 isolate. The limit of detection for the prototype strain ERBV1.1436/71 was 0.1 50% tissue culture infectious doses. The RT-PCR was used to detect viral RNA in six of 17 nasopharyngeal swab samples from horses that had clin...
Congenital diaphragmatic eventration in a stillborn foal. Jackson C, Collyer PB, Loynachan A.A stillborn full term foal was presented at necropsy. The dilated duodenum and the dorsal and ventral left colon and cecum extended into the thoracic cavity and were encased by a thin transparent membrane originating from the diaphragm. The congenital condition was diagnosed as a developmental anomaly with diaphragmatic eventration. To the authors' knowledge, this is the first report of diaphragmatic eventration in a Thoroughbred stillborn foal.
IdeE, an IgG-endopeptidase of Streptococcus equi ssp. equi.
FEMS microbiology letters    August 23, 2006   Volume 262, Issue 2 230-235 doi: 10.1111/j.1574-6968.2006.00404.x
Lannergård J, Guss B.Streptococcus equi ssp. equi is the causative agent of strangles, a highly contagious and serious disease in the upper respiratory tract of horses. The present study describes the characterization of IdeE, a homolog of the secreted IgG-specific protease IdeS/Mac of Streptococcus pyogenes. The activity of IdeE is compared with the activity of IdeZ, the corresponding enzyme of the closely related S. equi ssp. zooepidemicus. A study of the proteolytic activity of recombinant IdeE and IdeZ on IgG from a selection of mammals shows that only antibodies containing the substrate site of IdeS/Mac are c...
[Frequent deworming in horses; it usually does not do any good, but it often harms].
Tijdschrift voor diergeneeskunde    August 19, 2006   Volume 131, Issue 14-15 524-530 
Eysker M, van Doorn DC, Lems SN, Weteling A, Ploeger HW.Due to excessive and inappropriate use of dewormers anthelmintic resistance has developed as a significant problem in horse parasites in the Netherlands. Since it is unlikely that new classes of anthelmintics against horse nematodes will be introduced in the near future, it is important to use the present drugs wisely. Veterinarians should advice horse owners about worm control programs with a more targeted approach. The number of anthelmintic treatments should be reduced and, through selective anthelmintic treatments, further development of anthelmintic resistance should be delayed. Preferabl...
High-resolution gene maps of horse chromosomes 14 and 21: additional insights into evolution and rearrangements of HSA5 homologs in mammals.
Genomics    August 17, 2006   Volume 89, Issue 1 89-112 doi: 10.1016/j.ygeno.2006.06.012
Goh G, Raudsepp T, Durkin K, Wagner ML, Schäffer AA, Agarwala R, Tozaki T, Mickelson JR, Chowdhary BP.High-resolution physically ordered gene maps for equine homologs of human chromosome 5 (HSA5), viz., horse chromosomes 14 and 21 (ECA14 and ECA21), were generated by adding 179 new loci (131 gene-specific and 48 microsatellites) to the existing maps of the two chromosomes. The loci were mapped primarily by genotyping on a 5000-rad horse x hamster radiation hybrid panel, of which 28 were mapped by fluorescence in situ hybridization. The approximately fivefold increase in the number of mapped markers on the two chromosomes improves the average resolution of the map to 1 marker/0.9 Mb. The improv...
Cholesterol oxidase (ChoE) is not important in the virulence of Rhodococcus equi.
Veterinary microbiology    August 14, 2006   Volume 118, Issue 3-4 240-246 doi: 10.1016/j.vetmic.2006.08.006
Pei Y, Dupont C, Sydor T, Haas A, Prescott JF.To analyze further the role in virulence of the prominent cholesterol oxidase (ChoE) of Rhodococcus equi, an allelic exchange choE mutant from strain 103+ was constructed and assessed for virulence in macrophages, in mice, and in foals. There was no difference between the mutant and parent strain in cytotoxic activity for macrophages or in intra-macrophage multiplication. No evidence of attenuation was obtained in macrophages and in mice, but there was slight attenuation apparent in four intra-bronchially infected foals compared to infection of four foals with the virulent parent strain, based...
Purkinje cell apoptosis in arabian horses with cerebellar abiotrophy.
Journal of veterinary medicine. A, Physiology, pathology, clinical medicine    August 12, 2006   Volume 53, Issue 6 286-287 doi: 10.1111/j.1439-0442.2006.00836.x
Blanco A, Moyano R, Vivo J, Flores-Acuña R, Molina A, Blanco C, Monterde JG.Purkinje cerebellar cells were studied in three Arabian horses aged between 6 and 8 months with clinical disorders in their movements, tremors and ataxia; the occurrence of apoptosis in this cell population was investigated by the (terminal deoxynucleotidyl transferase biotin-dUTP nick-end labelling (TUNEL) method. Both optical and electron microscopical images showed a scant number of Purkinje cells, most of them with morphological features of apoptosis such as condensation of the nucleus and cytoplasm as well as segregation and fragmentation of the nucleus into apoptotic bodies. The TUNEL te...
A molecular approach to the identification of cytotoxic T-lymphocyte epitopes within equine herpesvirus 1.
The Journal of general virology    August 9, 2006   Volume 87, Issue Pt 9 2507-2515 doi: 10.1099/vir.0.82070-0
Kydd JH, Davis-Poynter NJ, Birch J, Hannant D, Minke J, Audonnet JC, Antczak DF, Ellis SA.Equine herpesvirus 1 (EHV-1) causes respiratory and neurological disease and abortion in horses. Animals with high frequencies of cytotoxic T lymphocytes (CTL) show reduced severity of respiratory disease and frequency of abortion, probably by CTL-mediated control of cell-associated viraemia. This study aimed to identify CTL epitopes restricted by selected major histocompatibility complex (MHC) class I alleles expressed in the equine leukocyte antigen (ELA) A3 haplotype. Effector CTL were induced from EHV-1-primed ponies and thoroughbreds with characterized MHC class I haplotypes and screened ...
Cryopreservation of horse semen under laboratory and field conditions using a Stirling Cycle freezer.
Cryo letters    August 8, 2006   Volume 27, Issue 3 179-186 
Faszer K, Draper D, Green JE, Morris GJ, Grout BW.A Stirling Cycle freezer has been developed as an alternative to conventional liquid nitrogen controlled rate freezers. Horse semen samples were cooled in 0.25 ml straws and 15 ml bags in the Stirling Cycle freezer under laboratory conditions and as a portable device, powered from a car battery. For comparison, straws were frozen in a conventional liquid nitrogen controlled rate freezer. Upon thawing, motility and viability of samples frozen in the Stirling Cycle freezer were not significantly different when compared to samples frozen in the liquid nitrogen freezer. Unlike liquid nitrogen syst...
Advanced techniques in the diagnosis and management of infectious pulmonary diseases in horses.
The Veterinary clinics of North America. Equine practice    August 3, 2006   Volume 22, Issue 2 633-xi doi: 10.1016/j.cveq.2006.03.001
Brown VA, Wilkins PA.Techniques for novel approaches to the diagnosis and management of equine pulmonary disease continue to be developed and used in clinical practice. Diagnostic techniques involving immunoassays and nucleic acid-based tests not only decrease the time in which results become available but increase the sensitivity and specificity of test results. These assays do not substitute for careful clinical evaluation but can shorten the time to a confirmed accurate diagnosis, and thus allow for early initiation of therapeutic strategies and prevention protocols. With further understanding of the molecular ...
Exclusion of linkage of the RYR1, CACNA1S, and ATP2A1 genes to recurrent exertional rhabdomyolysis in Thoroughbreds.
American journal of veterinary research    August 3, 2006   Volume 67, Issue 8 1395-1400 doi: 10.2460/ajvr.67.8.1395
Dranchak PK, Valberg SJ, Onan GW, Gallant EM, Binns MM, Swinburne JE, Mickelson JR.To determine whether there was genetic linkage between the recurrent exertional rhabdomyolysis (RER) trait in Thoroughbred horse pedigrees and DNA markers in genes (the sarcoplasmic reticulum calcium release channel [RYR1] gene, the sarcoplasmic reticulum calcium ATPase [ATP2A1] gene, and the transverse tubule dihydropyridine receptor-voltage sensor [CACNA1S] gene) that are important in myoplasmic calcium regulation. Methods: 34 horses in the University of Minnesota RER resource herd and 62 Thoroughbreds from 3 families of Thoroughbreds outside of the university in which RER-affected status wa...
The use of a random regression model to account for change in racing speed of German trotters with increasing age.
Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie    August 3, 2006   Volume 123, Issue 4 239-246 doi: 10.1111/j.1439-0388.2006.00596.x
Bugislaus AE, Roehe R, Willms F, Kalm E.In a genetic analysis of German trotters, the performance trait racing time per km was analysed by using a random regression model on six different age classes (2-, 3-, 4-, 5- and 6-year-old and older trotters; the age class of 3-year-old trotters was additionally divided by birth months of horses into two seasons). The best-fitting random regression model for the trait racing time per km on six age classes included as fixed effects sex, race track, condition of race track (fitted as second-order polynomial on age), distance of race and each driver (fitted as first-order polynomial on age) as ...
Gross, histologic, and gene expression characteristics of osteoarthritic articular cartilage of the metacarpal condyle of horses.
American journal of veterinary research    August 3, 2006   Volume 67, Issue 8 1299-1306 doi: 10.2460/ajvr.67.8.1299
Smith KJ, Bertone AL, Weisbrode SE, Radmacher M.To identify patterns and correlations of gross, histologic, and gene expression characteristics of articular cartilage from horses with osteoarthritis. Methods: 10 clinically normal horses and 11 horses with osteoarthritis of the metacarpal condyles. Methods: Metacarpophalangeal joints were opened and digitally photographed, and gross lesions were scored and quantified. Representative cartilage specimens were stained for histologic scoring. Total RNA from dorsal and palmar articular surfaces was processed on an equine gene expression microarray. Results: Histologic scores were greater in both ...
Evaluation of FOXC2 as a candidate gene for chronic progressive lymphedema in draft horses.
Veterinary journal (London, England : 1997)    August 1, 2006   Volume 174, Issue 2 397-399 doi: 10.1016/j.tvjl.2006.05.023
Young AE, Bower LP, Affolter VK, De Cock HE, Ferraro GL, Bannasch DL.Chronic progressive lymphedema (CPL) is a debilitating condition identified in Clydesdales, Shires and Belgian draft horses and results in progressive swelling of the lower legs associated with the development of thick skin folds, ulcerations, fibrosis and marked hyperkeratosis. The result is severe discomfort and recurrent secondary infection, often requiring euthanasia. Due to the delayed onset, many horses are bred prior to diagnosis. CPL has only been documented in three related draft horse breeds, suggesting a genetic cause. Determining the molecular basis would enable owners to test hors...
[PCR-RFLP analysis of the mtDNA Cytb gene in three different horse breeds].
Yi chuan = Hereditas    July 28, 2006   Volume 28, Issue 8 933-938 
Li JL, Shi YF, Bu RQ, Mang L.Restriction endonucleases, namely BamH I, Taq I, Hae III, Rsa I and Hinc II, were used to analyze the polymorphism of partial mtDNA Cytb gene sequences from 256 horses 6 types (Thoroughbred, Sanhe, Wuzhumuqin, Xinihe, Wushen and Pony) including the imported breed, cultivated breed and local breed. The products of endonuclease digestion were run on 8% non-denaturing polyacrylamide gel electrophoresis and detected by silver staining. Results indicated BamH I and Taq I polymorphism. In all 7 restriction patterns were defected that could be sorted into 3 haplotypes, of which haplotypes I and III w...
Development of the Lipizzan horse breed.
Reproduction in domestic animals = Zuchthygiene    July 28, 2006   Volume 41, Issue 4 280-285 doi: 10.1111/j.1439-0531.2006.00726.x
Dovc P, Kavar T, Sölkner H, Achmann R.The development and a brief history of the Lipizzan horse breed are reviewed. The contribution of several breeds, some of them already extinct, to the development of the Lipizzan horse, gives it a special status representing an important gene pool. This well-documented breed is a part of the common European natural and cultural heritage. Breeding practices establishing stallion and mare family lines as well as availability of pedigrees are described. Molecular analysis of mitochondrial DNA (mtDNA) and microsatellite data allowed us to analyse the structure of the Lipizzan population, to estima...
Derivation, maintenance, and induction of the differentiation in vitro of equine embryonic stem cells.
Methods in molecular biology (Clifton, N.J.)    July 19, 2006   Volume 329 59-79 doi: 10.1385/1-59745-037-5:59
Saito S, Sawai K, Minamihashi A, Ugai H, Murata T, Yokoyama KK.We describe here the isolation and maintenance of pluripotent embryonic stem (ES) cells from equine blastocysts that have been frozen and thawed. Equine ES cells appear to maintain a normal diploid karyotype in culture. These cells express markers that are characteristic of mouse ES cells, namely, alkaline phosphatase, stage-specific-embryonic antigen 1, STAT3, and Oct4. We also describe protocols for the induction of differentiation in vitro to neural precursor cells in the presence of basic fibroblast growth factor (bFGF), epidermal growth factor, and platelet-derived growth factor and to he...
Cloning and pharmacological characterization of the equine adenosine A3 receptor.
Journal of veterinary pharmacology and therapeutics    July 19, 2006   Volume 29, Issue 4 255-263 doi: 10.1111/j.1365-2885.2006.00748.x
Brandon CI, Vandenplas M, Dookwah H, Murray TF.The aim of this study was to establish a heterologous expression system for the equine adenosine A(3) receptor (eA(3)-R) in an effort to ascertain its pharmacologic profile. Initially, radioligand binding assays identified clones expressing the eA(3)-R in human embryonic kidney cells (HEK) based on the specific binding of [(125)I]AB-MECA. Subsequently, adenylate cyclase assays were utilized to demonstrate functional coupling of the eA(3)-R to the G-protein/adenylate cyclase system. Equilibrium competition binding assays were then performed using selective and non-selective A(3) agonists and an...
Myopathy with central cores in a foal.
Veterinary pathology    July 19, 2006   Volume 43, Issue 4 579-583 doi: 10.1354/vp.43-4-579
Paciello O, Pasolini MP, Navas L, Russo V, Papparella S.Central core disease is a nonprogressive or slowly progressive congenital myopathy with a variable degree of hypotonia and axial and proximal muscle weakness that is histologically characterized by areas devoid of oxidative enzyme activity, resulting from an absence or low numbers of mitochondria in these regions (central core). A 10-month-old, male, pony foal was examined because of stiff gait, marked contractures of the distal portion of the limbs, flexion deformities of the hooves, and moderate hypotonia that had been present from birth. The foal had increased creatine kinase (282 U/liter; ...
Diagnostic challenge: lethargy and weakness in an Arabian foal with cardiac murmurs. Ventricular septal defect (VSD).
Australian veterinary journal    July 11, 2006   Volume 84, Issue 6 209-212 doi: 10.1111/j.1751-0813.2006.tb12801.x
Hughes KJ.No abstract available
Polymorphism identification, RH mapping, and association analysis with the anxiety trait of the equine serotonin transporter (SLC6A4) gene.
The Journal of veterinary medical science    July 6, 2006   Volume 68, Issue 6 619-621 doi: 10.1292/jvms.68.619
Momozawa Y, Takeuchi Y, Tozaki T, Kikusui T, Hasegawa T, Raudsepp T, Chowdhary BP, Kusunose R, Mori Y.Equine anxiety trait is considered an important temperament in various situations, including riding, training, and daily care. This study examined the polymorphism of the equine serotonin transporter (SLC6A4) gene as a candidate genetic element influencing equine anxiety trait. The sequence of the coding region of this gene was highly homologous with those of other mammals, and four single nucleotide polymorphisms were found by comparing the sequences of ten genetically unrelated thoroughbred horses. Radiation hybrid mapping revealed that this gene was located 26.92 cR from neurofibromin 1 on ...
Nucleotide structure of equine platelet-derived growth factor-A and -B and expression in horses with induced acute tendinitis.
American journal of veterinary research    July 5, 2006   Volume 67, Issue 7 1218-1225 doi: 10.2460/ajvr.67.7.1218
Donnelly BP, Nixon AJ, Haupt JL, Dahlgren LA.To characterize the nucleotide sequence of equine platelet-derived growth factor (PDGF)-A and -B and analyze temporal expression of these genes in equine tendon after induced tendinitis injury. Animals-18 mature horses. Methods: Genes for equine PDGF-A and -B were reverse transcribed and sequenced from synovial tissue mRNA obtained from a 3-year-old horse. Collagenase-induced lesions were created in the tensile region of the superficial digital flexor tendon in 14 horses; 3 horses served as uninjured control animals. Tendons were harvested and total RNA was isolated from experimental horses 1,...
Evaluation of permissiveness and cytotoxic effects in equine chondrocytes, synovial cells, and stem cells in response to infection with adenovirus 5 vectors for gene delivery.
American journal of veterinary research    July 5, 2006   Volume 67, Issue 7 1145-1155 doi: 10.2460/ajvr.67.7.1145
Ishihara A, Zachos TA, Bartlett JS, Bertone AL.To evaluate host cell permissiveness and cytotoxic effects of recombinant and modified adenoviral vectors in equine chondrocytes, synovial cells, and bone marrow-derived mesenchymal stem cells (BMD-MSCs). Methods: Articular cartilage, synovium, and bone marrow from 15 adult horses. Methods: Equine chondrocytes, synovial cells, and BMD-MSCs and human carcinoma (HeLa) cells were cultured and infected with an E-1-deficient adenovirus vector encoding the beta-galactosidase gene or the green fluorescent protein gene (Ad-GFP) and with a modified E-1-deficient vector with the arg-gly-asp capsid pepti...
Clinical, cytogenetic and hormonal findings in a stallion with hypospadias–a case report.
Veterinary journal (London, England : 1997)    July 3, 2006   Volume 173, Issue 3 679-682 doi: 10.1016/j.tvjl.2006.03.005
Bleul U, Theiss F, Rütten M, Kähn W.This case report describes a three-year-old Friesian stallion with hypospadias. Physical examination revealed a ventrocaudal deviation of the shaft of the penis and an incomplete glans penis. The urethral opening was 4 cm in length, slit-like and had a mucous membrane covering. A short fold ran from the ventral aspect of the anus and ended with a non-pigmented hairless area of skin. A human choriongonadotropin (hCG)-stimulation test resulted in an increase in the plasma levels of estrogen sulfate and testosterone, indistinguishable from that of a normal stallion. The karyogram had a normal num...
Sebaceous adenitis in a 7-year-old Arabian gelding.
The Canadian veterinary journal = La revue veterinaire canadienne    July 1, 2006   Volume 47, Issue 6 583-586 
Osborne C.A 7-year-old Arabian gelding was presented with a 9-month history of progressive patches of nonpruritic scaling, crusting, alopecia, and leukoderma of the periocular areas and muzzle, becoming generalized over time. Sebaceous adenitis was diagnosed on histopathologic examination. Lesions resolved without treatment, coinciding with regression of a sarcoid on the neck. Un cheval Arabe castré âgé de 7 ans a été présenté pour une histoire de 9 mois de plaques de desquamation, de croutes, d’alopécie et de leucodermie sur les régions périoculaire et sur le nez, devenant généralisées ...
[Elevation of IFN-gamma transcription level in peripheral blood mononuclear cells of EIAV vaccinated horses]. Wang Y, Zhang XY, Wei LL, Wu DL, Wang XJ, Xiang WH, Shen RX, Shao YM.To evaluate the relationship between the transcriptional level of IFN-gamma mRNA in peripheral blood mononuclear cells (PBMC) and immune protective response driven by inoculated horses with donkey leukocyte attenuated vaccine of EIAV(DLV), and to elucidate the immune mechanism of DLV. Methods: A real-time PCR method was established for quantitative detection of IFN-gamma mRNA level from horse PBMCs. Twelve horses were divided into vaccination group, healthy control group, challenging control group and EIAV natural infection group. The transcriptional level and distribution of IFN-gamma mRNA in...
Morphological evolution and heritability estimates for some biometric traits in the Murgese horse breed.
Genetics and molecular research : GMR    June 30, 2006   Volume 5, Issue 2 309-314 
Dario C, Carnicella D, Dario M, Bufano G.A data set concerning 1,816 subjects entered in the Italian Horse Registry from 1925 to 2002 was analyzed to investigate the morphological evolution of the Murgese horse and to obtain useful elements to enhance breeding practices. Three basic body measurements (height at withers, chest girth, and cannon bone circumference) were considered for each subject. Heritabilities were calculated for each parameter to infer the growth and development traits of this breed. Over the past 20 years the Murgese horse has undergone considerable changes, passing from a typical mesomorphic structure (height at ...
von Willebrand factor A1 domain can adequately substitute for A3 domain in recruitment of flowing platelets to collagen.
Journal of thrombosis and haemostasis : JTH    June 29, 2006   Volume 4, Issue 10 2151-2161 doi: 10.1111/j.1538-7836.2006.02111.x
Bonnefoy A, Romijn RA, Vandervoort PA, VAN Rompaey I, Vermylen J, Hoylaerts MF.Binding of von Willebrand factor (VWF) to platelet GPIbalpha and to collagen is attributed to VWF A1 and A3 domains, respectively. Objective: Using VWF, VWF lacking A1 (DeltaA1-VWF) or A3 (DeltaA3-VWF) and VWF with defective A3 (H1786A-VWF), in combination with recombinant A1 (residues 1262-1492) or A3 (residues 1671-1878), fused to glutathione-S-transferase (GST-A1 and GST-A3), we have re-investigated the role of A1 in platelet recruitment to surfaces of collagen. Results: In flow, measurable binding of DeltaA3-VWF occurred to horse tendon, but also to human type III collagen. GST-A1 and GST-...
Age-related expression of molecular regulators of hypertrophy and maturation in articular cartilage.
Journal of orthopaedic research : official publication of the Orthopaedic Research Society    June 22, 2006   Volume 24, Issue 8 1773-1781 doi: 10.1002/jor.20227
Semevolos SA, Nixon AJ, Fortier LA, Strassheim ML, Haupt J.The purpose of this study was to determine changes in the expression of regulatory molecules in normal equine articular cartilage throughout development up to 18 months of age. The hypothesis was that expression of these regulatory molecules would decrease from birth to postpubescence. Cartilage was harvested from normal femoropatellar or scapulohumeral joints from 34 fresh horse cadavers. Horses were placed in four age groups [prenatal (n = 5); prepubertal, 0-6 months (n = 11); pubertal, 7-14 months (n = 13); and postpubertal, 15-18 months (n = 5)]. Indian hedgehog (Ihh), Gli1, Gli3, Patched1...