Investigation of the Multiple Malformation Syndrome in Llamas and Alpacas Associated with Choanal Atresia

This study is administered through MAF and completely funded by ARF

Investigation of the Multiple Malformation Syndrome in Llamas and Alpacas Associated with Choanal Atresia

Principal investigators:

Anibal G. Armien, DVM, MSc
Kent M. Reed, PhD
University of Minnesota College of Veterinary Medicine

Choanal atresia (CA) is a common inherited congenital disease affecting alpacas and llamas. It is caused by abnormal development of the nasal passages, which prevents airflow from the nose to the larynx. The condition results in open-mouth breathing in newborns and predisposes them to fatal aspiration pneumonia. Recent scientific evidence indicates that CA is similar to CHARGE syndrome in humans, for which the genetic mutation (CDH7) has been identified. Humans affected with CHARGE syndrome are often born with life-threatening birth defects, including heart deformities and breathing problems. In this study, scientists from the University of Minnesota tried to determine whether CDH7 is associated with CA in alpacas and llamas but found that complete sequencing of the CHD7 gene will be needed to determine if other mutations in the gene are the cause of CA in llamas and alpacas. Preliminary data indicate that nine of 10 alpacas with CA have cranial and/or internal organ malformation. Researchers identified patterns of malformation that are associated with CA in these animals, and the findings will provide veterinarians with a better way to diagnose CA and differentiate it from other diseases.

The abstracts below are from publications resulting from this work.

Genome. 2010 Mar;53(3):224-30. doi: 10.1139/g09-100.

A candidate gene for choanal atresia in alpaca.


Reed KM, Bauer MM, Mendoza KM, Armién AG.

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 2x 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.

Vet J. 2013 Oct;198(1):295-8. doi: 10.1016/j.tvjl.2013.07.006. Epub 2013 Aug 9.

Evaluation of CHD7 as a candidate gene for choanal atresia in alpacas (Vicugna pacos).


Reed KM, Mendoza KM, Fleege EC, Damerow JA, Armién AG.

Choanal atresia (CA) is a craniofacial malformation characterized by obstruction of the posterior nasal aperture, resulting in laborious respiratory inspiration and exhalation. Alpaca crias with CA typically develop fatal pneumonia, frequently as the result of milk aspiration during nursing, and euthanasia is usually inevitable. Nonsense or missense mutations in the CHD7 gene cause a comparable condition (CHARGE syndrome) in humans. In this study, the coding region of CHD7 was sequenced in six CA-affected alpacas. Forty-nine sequence variants were identified, of which 10 would result in amino acid changes (non-synonymous), some with potentially deleterious effects. However, none of the observed variants would result in the obvious deleterious effects caused by nonsense or missense mutations. Although a role for CHD7 mutations in CA cannot be definitively dismissed, these do not appear to be the primary cause of CA in alpacas.