Molecular analyses of a tyrosinase-negative albino family

Journal Article · Mon Feb 01 04:00:00 EST 1993 · American Journal of Human Genetics; (United States)

OSTI ID:6572666

Park, K C; Chintamaneni, C D; Kwon, B S ^[1]; Halaban, R ^[2]; Witkop, Jr, C J ^[3]

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1. Indiana Univ., Indianapolis (United States)
2. Yale Univ., New Haven, CT (United States)
3. Univ. of Minnesota, Minneapolis (United States)

Sequence analysis of the tyrosinase coding region from an individual with tyrosinase-negative oculocutaneous albinism revealed that the patient was a compound heterozygote. One allele carried a C[r arrow]A single-base substitution in codon 355 of exon 3, and the other carried a two-nucleotide deletion in exon 1. The nucleotide substitution caused a putative amino acid change from threonine (ACA) to lysine (AAA), abolishing a signal for N-glycosylation. The two base-pair deletion caused a frameshift, creating a putative premature termination signal at codon 226. The melanocytes from the proband and her affected brother were amelanotic and devoid of measurable tyrosinase activity. Moreover, gel electrophoretic analysis of the immunoprecipitated proband tyrosinase showed that the protein was no processed to the mature glycosylated form, confirming the predicted consequence of the amino acid change. The two-base deletion on the homologous allele was detected only by sequencing genomic DNA. The transcript of this allele was not represented in the cDNA library and could not be detected by PCR mRNA, and the putative truncated protein ([approximately]25 kDa) was not present in immunoprecipitates, suggesting that the allele with the missense mutation may be preferentially expressed. 29 refs., 6 figs., 1 tab.

• OSTI ID: 6572666
• Journal Information: American Journal of Human Genetics; (United States), Journal Name: American Journal of Human Genetics; (United States) Vol. 52:2; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMAL CELLS
CARBOXYLIC ACIDS
ELECTROPHORESIS
ENZYMES
GENE MUTATIONS
GLYCOPROTEINS
HYDROXY ACIDS
HYDROXY COMPOUNDS
HYDROXYLASES
LYSINE
MELANIN
MUTATIONS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXIDOREDUCTASES
PIGMENTS
PROTEINS
THREONINE
TYROSINASE