A family of rapidly evolving genes from the sex reversal critical region in Xp21.
Patients with an intact SRY gene and duplications of portions of Xp21 develop as phenotypic females. We have recently mapped this sex reversal locus, DSS, to a 160-kb region of Xp21 that includes the adrenal hypoplasia congenita locus. To clone the gene(s) underlying DSS and AHC, we isolated expressed sequences from the region. Here we describe the characterization of two related genes. DAM10 and DAM6, expressed in adult testis and lung tumors. The predicted DAM10 and DAM6 proteins are 66% identical and are both highly similar to the MAGE family of tumor-associated antigens and to mouse necdin. Genes belonging to the MAGE superfamily, DAMs, MAGEs, and necdin, are likely to have originated from a common ancestor and to be subject to an unusually rapid evolution. The tumor-restricted expression of DAM proteins and their structural similarity to MAGE genes suggest that DAM peptides may be targets for active immunotherapy in lung cancer patients.
Dabovic
B
B
Biologia Generale e Genetica Medica, Università di Pavia, Italy.
Zanaria
E
E
Bardoni
B
B
Lisa
A
A
Bordignon
C
C
Russo
V
V
Matessi
C
C
Traversari
C
C
Camerino
G
G
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics; D001483:Base Sequence; D005075:Biological Evolution; D057137:DAX-1 Orphan Nuclear Receptor; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D018168:Receptors, Retinoic Acid / Q000235:genetics; D012097:Repressor Proteins; D012733:Sex Differentiation / Q000235:genetics*; D051876:Sex-Determining Region Y Protein; D013737:Testis / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics; D014960:X Chromosome
D000951:Antigens, Neoplasm; D057137:DAX-1 Orphan Nuclear Receptor; D017931:DNA Primers; D004268:DNA-Binding Proteins; C097488:MAGEB1 protein, human; C072012:MAGEB2 protein, human; C512965:Mageb2 protein, mouse; C539965:NR0B1 protein, human; D009363:Neoplasm Proteins; C539966:Nr0b1 protein, mouse; D009687:Nuclear Proteins; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; C497746:Sry protein, mouse; D014157:Transcription Factors