Although sled dogs are one of the most specialized groups of dogs, their origin and evolution has received much less attention than many other dog groups. We applied a genomic approach to investigate their spatiotemporal emergence by sequencing the genomes of 10 modern Greenland sled dogs, an ~9500-year-old Siberian dog associated with archaeological evidence for sled technology, and an ~33,000-year-old Siberian wolf. We found noteworthy genetic similarity between the ancient dog and modern sled dogs. We detected gene flow from Pleistocene Siberian wolves, but not modern American wolves, to present-day sled dogs. The results indicate that the major ancestry of modern sled dogs traces back to Siberia, where sled dog-specific haplotypes of genes that potentially relate to Arctic adaptation were established by 9500 years ago.
Matched MeSH terms: Mitochondrial Membrane Transport Proteins/genetics
Citrin deficiency is an autosomal recessive disorder caused by mutation in the SLC25AJ3 gene. It has two major phenotypes: adult-onset type II citrullinemia (CTLN2) and neonatal intrahepatic cholestatic caused by citrin deficiency (NICCD). NICCD is characterized by neonatal/infantile-onset cholestatic hepatitis syndrome associated with multiple amino acidemia and hypergalactosemia. NICCD is self-limiting in most patients. However, some patients may develop CTLN2 years later, which manifests as fatal hyperammonemia coma. We report three unrelated Malay children with genetically confirmed NICCD characterised by an insertion mutation IVS16ins3kb in SLC25A13 gene. All 3 patients presented with prolonged neonatal jaundice which resolved without specific treatment between 5 to 10 months. Of note was the manifestation of a peculiar dislike of sweet foods and drinks. Elevated plasma citrulline was an important biochemical marker. NICCD should be considered in the differential diagnosis of cholestatic jaundice in Malaysian infants regardless of ethnic origin.
Matched MeSH terms: Mitochondrial Membrane Transport Proteins/genetics*
We report two Malaysian siblings with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). The younger sibling, a six-month-old Chinese girl, presented with prolonged neonatal jaundice, and was investigated for biliary atresia. Urine metabolic screen showed the presence of urinary-reducing sugars, and she was treated with a lactose-free formula. NICCD was suspected based on the clinical history, examination and presence of urinary citrulline. Mutation study of the SLC25A13 gene showed the compound heterozygotes, 851del4 and IVS16ins3kb, which confirmed the diagnosis of NICCD in the patient and her three-year-old female sibling, who also had unexplained neonatal cholestasis. Long-term dietary advice, medical surveillance and genetic counselling were provided to the family. The diagnosis of NICCD should be considered in infants with unexplained prolonged jaundice. DNA-based genetic testing of the SLC25A13 gene may be performed to confirm the diagnosis retrospectively. An awareness of this condition may help in early diagnosis using appropriate metabolic and biochemical investigations, thus avoiding invasive investigations in infants with neonatal cholestasis caused by NICCD.
Matched MeSH terms: Mitochondrial Membrane Transport Proteins/genetics*
The human SLC25A13 gene encodes citrin, the liver-type mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), and SLC25A13 mutations cause citrin deficiency (CD), a disease entity that encompasses different age-dependant clinical phenotypes such as Adult-onset Citrullinemia Type II (CTLN2) and Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency (NICCD). The analyses of SLC25A13 gene and its protein/mRNA products remain reliable tools for the definitive diagnoses of CD patients, and so far, the SLC25A13 mutation spectrum in Chinese CD patients has not been well-characterized yet.
Matched MeSH terms: Mitochondrial Membrane Transport Proteins/genetics*
Citrin deficiency, aetiologically linked to mutations of SLC25A13 gene, has two clinical phenotypes, namely adult-onset type II citrullinaemia (CTLN2) and neonatal/infantile intrahepatic cholestasis, caused by citrin deficiency (NICCD). Malaysian patients with NICCD, especially of Malay and East Malaysian indigenous descent, have never been reported in the literature. We present the clinical features, biochemical findings and results of molecular analysis in 11 Malaysian children with NICCD. In this case series, all patients manifested prolonged cholestatic jaundice and elevated citrulline levels. The other more variable features included failure to thrive, bleeding diathesis, hypoproteinaemia, abnormal liver enzymes, prolonged coagulation profile, hyperammonaemia, hypergalactosaemia, multiple aminoacidaemia, elevated α-feto protein and urinary orotic acid as well as liver biopsies showing hepatitis and steatosis. DNA analysis of SLC25A13 revealed combinations of 851del4(Ex9), IVS16ins3kb and 1638ins23. Most of our patients recovered completely by the age of 22 months. However, one patient had ongoing symptoms at the time of reporting and one had died of liver failure. Since a small percentage of children with NICCD will develop CTLN2 and the mechanisms leading to this is yet to be defined, ongoing health surveillance into adulthood is essential.
Matched MeSH terms: Mitochondrial Membrane Transport Proteins/genetics