title: Mutational spectrum of the TYR and SLC45A2 genes in Pakistani families with oculocutaneous albinism, and potential founder effect of missense substitution (p.Arg77Gln) of tyrosinase.
abstract: BACKGROUND
  Oculocutaneous albinism (OCA) is an autosomal recessive disorder of abnormal melanin formation, which results in hypopigmentation of skin, hair and eyes. OCA is classified into four types based on clinical and genetic findings. OCA1 is the most severe form of albinism, and is caused by mutations in the tyrosinase (TYR) gene, while OCA4 is caused due to mutations in SLC45A2.
  
  
  METHODS
  In total, 13 families with ≥ 3 members with OCA were enrolled. Family history was ascertained and pedigrees were drawn up. Blood samples were collected and processed for DNA extraction. Linkage analysis was performed by typing three short tandem repeat markers in candidate regions of TYR and SLC45A2. Sequence analysis was performed of all the coding exons and adjacent intronic sequences of both genes.
  
  
  RESULTS
  Eight families showed linkage to OCA1 and one family showed linkage to OCA4. Four missense substitutions (p.Arg239Trp, p.Ser192Tyr, p.Ser44Arg and p.Arg77Gln) were identified in TYR in the families with OCA1 linkage, and another missense substitution (p.Gln272Lys) was identified in the family with OCA4 linkage. One of the identified missense substitution (p.Arg77Gln) in TYR was found in five different families, which had a common haplotype.
  
  
  CONCLUSIONS
  We identified four missense substitutions in TYR and a single missense substitution in SLC45A2. One missense substitution (p.Arg77Gln) in TYR was found in five different families that originated from the same geographical area and displayed a common haplotype, suggesting a single origin that then spread to different geographical areas of Azad Kashmir, Pakistan.
authors.affiliation: Institute of Biochemistry and Biotechnology (IBBt), UVAS, Lahore, Pakistan.
authors.forename: S A
authors.initials: SA
authors.lastname: Shah
authors.affiliation: Medical Centre, Balochistan University of Information Technology, Engineering and Management Sciences (BUITEMS), Quetta, Pakistan.
authors.forename: N
authors.initials: N
authors.lastname: Raheem
authors.affiliation: Department of Biotechnology and Informatics, BUITEMS, Quetta, Pakistan.
authors.forename: S
authors.initials: S
authors.lastname: Daud
authors.affiliation: Institute of Biochemistry and Biotechnology (IBBt), UVAS, Lahore, Pakistan.
authors.forename: J
authors.initials: J
authors.lastname: Mubeen
authors.affiliation: Department of Computer Sciences, BUITEMS, Quetta, Pakistan.
authors.forename: A A
authors.initials: AA
authors.lastname: Shaikh
authors.affiliation: Department of Biotechnology and Informatics, BUITEMS, Quetta, Pakistan.
authors.forename: A H
authors.initials: AH
authors.lastname: Baloch
authors.affiliation: Institute of Biochemistry and Biotechnology (IBBt), UVAS, Lahore, Pakistan.
authors.forename: A
authors.initials: A
authors.lastname: Nadeem
authors.affiliation: Institute of Biochemistry and Biotechnology (IBBt), UVAS, Lahore, Pakistan.
authors.forename: M
authors.initials: M
authors.lastname: Tayyab
authors.affiliation: Department of Livestock Production, Faculty of Animal Production and Technology, University of Veterinary and Animal Sciences (UVAS), Lahore, Pakistan.
authors.forename: M E
authors.initials: ME
authors.lastname: Babar
authors.affiliation: Department of Biotechnology and Informatics, BUITEMS, Quetta, Pakistan.
authors.forename: J
authors.initials: J
authors.lastname: Ahmad
mesh_terms: D000293:Adolescent; D000328:Adult; D016115:Albinism, Oculocutaneous / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D018703:Founder Effect; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D014442:Monophenol Monooxygenase / Q000235:genetics*; D020125:Mutation, Missense; D010154:Pakistan; D010375:Pedigree; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D026901:Membrane Transport Proteins; C510061:SLC45A2 protein, human; D014442:Monophenol Monooxygenase