engleski

Large-scale mitogenome sequencing as a strategy to iden-tify mitochondrial genetic disorders in domestic animals: Cattle mitogenome sequencing as a proof of the concept

Mitochondrial DNA (mtDNA) is crucial for the aerobic respira-tion while among many functions it contribute to cellular activities such as are apoptosis, iron storage, calcium homeostasis, hormone signaling/synthesis and thermogenesis. Considerable efforts in human medicine resulted in identification of several disorders caused by dysfunctional mitochondrial mutations. In contrast to humans, no single mitochondri-al disorder has been reported in cattle so far. Here we presented a case study where we performed large scale mitogenome sequencing in cattle (>800 individuals, > 120 breeds), together with screening for the hu-man known detrimental mitogenome mutations. Among several mildly detrimental mutations located in the NADH dehydrogenase gene com-plex, we have identified 2 mutations, one in Cika (T10663C in ND4L gene) and the other in Croatian Buša (C4171A in ND1 gene) cattle, each known to cause Leber’s Hereditary Optic Neuropathy (LHON) in humans. After anamnesis and clinical inspection of some individu-als within “detrimental mitolineage” of Cika cattle, one cow has clear symptoms of exophthalmia, a well-known consequence of the same mutation in humans. Here, we further discuss algorithmic (Magellan software) and molecular strategies that can increase cost-efficiency in identifying harmful mitogenome mutations in domestic animal popula-tions. Such efforts will enable establishment of animal models that will contribute to the better understanding of mitogenome disorders as well as to the breeding of healthier animals.

cattle and related species, functional genomics, high-throughput sequencing, genetic disorder, animal health

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