ABCMdb

PMID: 11138003

Lee MH, Lu K, Hazard S, Yu H, Shulenin S, Hidaka H, Kojima H, Allikmets R, Sakuma N, Pegoraro R, Srivastava AK, Salen G, Dean M, Patel SB
Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption.
Nat Genet. 2001 Jan;27(1):79-83., [PubMed]

Sentences

No. Mutations Sentence Comment

29 ABCG5 p.Arg419His ABCG5 p.Arg408* ABCG5 p.Arg243* ABCG5 p.Arg389His ABCG5 p.Arg419Pro We identified five point mutations: R243X (exon 6, proband 25), R389H (exon 9, probands 46, 113 and 146), R408X (exon 9, proband 140), R419H (exon 9, probands 40 and 132) and R419P (exon 9, proband 157) (Fig. 2a). Login to comment 35 ABCG5 p.Arg419His ABCG5 p.Arg408* ABCG5 p.Arg243* ABCG5 p.Arg389His Mutations resulting in R243X, R408X, R389H and R419H/P altered cleavage sites of restriction enzymes. Login to comment 36 ABCG5 p.Arg243* R243X mutation segregated with disease in pedigree 500; both parents are carriers and both affected children are homozygous (Fig. 2a) for the mutation. Login to comment 37 ABCG5 p.Arg408* Similarly, correlations are observed with other mutations (Fig. 2), except R408X, in which the mutation was found in a single individual whose parents were not available for analysis. Login to comment 46 ABCG5 p.Arg243* Mutation R243X (left-hand panels) results in a gain of the AlwnI site. Login to comment 48 ABCG5 p.Arg419Pro Similarly, mutation R419P causes a loss of the second BstUI site and can be shown to segregate appropriately in pedigree 4000 (right-hand panels). Login to comment 49 ABCG5 p.Arg419His BstUI can also be used to screen for R419H (data not shown). Login to comment 50 ABCG5 p.Arg389His Additionally, the first BstUI site is altered by mutation R389H (middle right panels). Login to comment 52 ABCG5 p.Arg408* Mutation R408X alters AvaI site (middle left panels). Login to comment 62 ABCG5 p.Arg419His ABCG5 p.Arg419His ABCG5 p.Arg243* ABCG5 p.Arg243* ABCG5 p.Arg389His ABCG5 p.Arg389His ABCG5 p.Arg419Pro ABCG5 p.Arg419Pro ABCG5 p.Gln604Glu ABCG5 p.Gln604Glu letter 80 nature genetics • volume 27 • january 2001 A G G A A C T G A A T T Arg Asn stop Ile C G A Arg A G G A A C A T Tnormal proband 25 T G AG T C A G CC G G Arg Val stop Ser C G A Arg C G GG T C A G Cnormal proband 140 100 200 300 400 bp 500 M C2C2+ 146 C1+ 113 132 140 41 46 63 M 100 200 300 400 500 bp M 41 46 63 113 132 140 146 C1+ C2+ C2- M AlwNI CAGNNNCTG 1 272 normal 135 141 proband 25 bp bp Ava I CPyCGPuG normal 199 109 proband 140 166 33 109 100 200 300 400 bp 500 100 200 300 400 500 M 22 23 24 25 26 27 C1+ C2+ M bp C2- 500 22 23 M 155 157 158 159 160 C1+ C2+ C2- M 155 156 4000 C C C G T AG A CC A G Gln Asp Pro Val C G C Arg C A G G A C G T A Proband 157 Normal BstUI CGCG 112 196 probands 41, 132, 157 92 normal 112 104 probands 46, 113, 146 204 104 normal 112 10492 exon 6 R243* exon 9 R408* exon 9 R389H exon 9 R419P BstUI CGCG bp bp bp bp bp bp proband 146 C T TC T CC A TA C G Thr His Leu Leu Arg normal C T TC T CC G TA C G 1 GCTCCGGGAA AACCAC---- CTGGGGACCT T--------- -------CCT 50 wild-type 1 GCTCCGGGAA AACCACGCTG CTGGACGCCA TGTCCGGGAG GCTGGGGCGC 50 51 GGGGGGTCCT TCCTGGGGGA GGTGTATGTG AACGGCCGGG CGCTGCGCCG 100 51 GCGGGGACCT TCCTGGGGGA GGTGTATGTG AACGGCCGGG CGCTGCGCCG 100 proband wild-type proband wild-type proband 101 GGAGCAGTTC CAGGACTGCT TCTCCTACGT CCTGCAG... .......... 150101 GGAGCAGTTC CAGGACTGCT TCTCCTACGT CCTGCAG... .......... 150 M wt+mut 63 64 65 66 67 C1 C2 M 61 62 mut wt wt + mut 200bp 400bp 500bp 1 2 3 4 5 6 7 8 9 10 Table 1 • Frequency of nucleotide changes in unrelated Japanese and North Americans of European descent Nucleotide change Predicted consequences Carrier frequency Restriction endonuclease changes C167T P9P not screened gain of BstNI site ∆20 bp at 402 frameshift & truncated protein no carriers in 55 Japanese controls - C867T R243X not screened gain of AlwNI site G1306A R389H no carriers in 145 Japanese and 156 Caucasians Loss of BstUI site C1362T R408X not screened loss of AvaI site G1396A R419H no carriers in 145 Japanese and 156 Caucasians Loss of BstUI site G1396C R419P no carriers in 145 Japanese and 156 Caucasians Loss of BstUI site C1950G Q604E 36% carriers in Caucasians loss of SmlI site Mutations (R243X, R408X, and R419H/P) or polymorphism Q604E were screened in unrelated Japanese and North Americans of European descent, using the restriction assays described in Fig. 2. Login to comment 91 ABCG5 p.Gln604Glu The polymorphic variant, Q604E (open circle) is also within this loop. Login to comment