Glycogen Branching Enzyme Deficiency (GBED), a fatal condition recently identified in fetuses and neonatal foals of the Quarter Horse and Paint Horse lineages, is caused by a nonsense mutation in codon 34 of the GBE1 gene, which prevents the synthesis of a functional GBE protein and severely disrupts glycogen metabolism. The aims of this project were to determine the mutant GBE1 allele frequency in random samples from the major relevant horse breeds, as well as the frequency with which GBED is associated with abortion and early neonatal death using the tissue archives from veterinary diagnostic laboratories. The mutant GBE1 allele frequency in registered Quarter Horse, Paint Horse, and Thoroughbred populations was 0.041, 0.036, and 0.000, respectively. Approximately 2.5% of fetal and early neonatal deaths in Quarter Horse-related breeds submitted to 2 different US diagnostic laboratories were homozygous for the mutant GBE1 allele, with the majority of these being abortions. Retrospective histopathology of the homozygotes detected periodic acid Schiff's (PAS)-positive inclusions in the cardiac or skeletal muscle, which is characteristic of GBED, in 8 out of the 9 cases. Pedigree and genotype analyses supported the hypothesis that GBED is inherited as a simple recessive trait from a single founder. The frequency with which GBED is associated with abortion and neonatal mortality in Quarter Horse-related breeds makes the DNA-based test valuable in determining specific diagnoses and designing matings that avoid conception of a GBED foal.

The MHC of the turkey (Meleagris gallopavo) is divided into two genetically unlinked regions; the MHC-B and MHC-Y. Although previous studies found the turkey MHC-B to be highly similar to that of the chicken, little is known of the gene content and extent of the MHC-Y. This study describes two partially overlapping large-insert BAC clones that genetically and physically map to the turkey MHC chromosome (MGA18) but to a region that assorts independently of MHC-B. Within the sequence assembly, 14 genes were predicted including new class I- and class IIB-like loci. Additional unassembled sequences corresponded to multiple copies of the ribosomal RNA repeat unit (18S-5.8S-28S). Thus, this newly identified MHC region appears to represent a physical boundary of the turkey MHC-Y. High-resolution multi-color fluorescence in situ hybridization studies confirm rearrangement of MGA18 relative to the orthologous chicken chromosome (GGA16) in regard to chromosome architecture, but not gene order. The difference in centromere position between the species is indicative of multiple chromosome rearrangements or alternate events such as neocentromere formation/centromere inactivation in the evolution of the MHC chromosome. Comparative sequencing of commercial turkeys (six amplicons totaling 7.6 kb) identified 68 single nucleotide variants defining nine MHC-Y haplotypes. Sequences of the new class I- and class IIB-like genes are most similar to MHC-Y genes in the chicken. All three loci are expressed in the spleen. Differential transcription of the MHC-Y class IIB-like loci was evident as one class IIB-like locus was only expressed in some individuals.

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Choanal atresia (CA) is a common nasal craniofacial malformation in New World domestic camelids (alpaca and llama). CA results from abnormal development of the nasal passages and is especially debilitating to newborn crias. CA in camelids shares many of the clinical manifestations of a similar condition in humans (CHARGE syndrome). Herein we report on the regulatory gene CHD7 of alpaca, whose homologue in humans is most frequently associated with CHARGE. Sequence of the CHD7 coding region was obtained from a non-affected cria. The complete coding region was 9003 bp, corresponding to a translated amino acid sequence of 3000 aa. Additional genomic sequences corresponding to a significant portion of the CHD7 gene were identified and assembled from the 2× alpaca whole genome sequence, providing confirmatory sequence for much of the CHD7 coding region. The alpaca CHD7 mRNA sequence was 97.9% similar to the human sequence, with the greatest sequence difference being an insertion in exon 38 that results in a polyalanine repeat (A12). Polymorphism in this repeat was tested for association with CA in alpaca by cloning and sequencing the repeat from both affected and non-affected individuals. Variation in length of the poly-A repeat was not associated with CA. Complete sequencing of the CHD7 gene will be necessary to determine whether other mutations in CHD7 are the cause of CA in camelids.