Читать книгу Pathology of Genetically Engineered and Other Mutant Mice - Группа авторов - Страница 31
Sanger Mouse SNP Database (https://www.sanger.ac.uk/sanger/Mouse_SnpViewer/rel‐1505)
ОглавлениеThis is similar to the MGI SNP database but provides specific annotation on a more limited number of inbred strains. This resource has sequence data on 36 inbred strains representing strains most commonly used in biomedical research today to those with great genetic diversity [38, 39]. The strains were sequenced and annotated, and base changes, relative to the C57BL/6J reference strain as well as predicted effect of changes are listed. This information can be useful when one suspects a molecular difference in a gene in an inbred strain with a specific lesion associated with a known genetic mutation. One example came from the observation of ectopic mineralization in several inbred mouse strains in an aging study that resembled, to various degrees, lesions observed in B6.Cg‐Abcc6tm1Jfk (ATP‐binding cassette, sub‐family C [CFTR/MRP], member 6) null mice, a mouse model for human pseudoxanthoma elasticum (PXE) [40]. Four strains were found to have the same SNP in the Abcc6 gene that was predicted to have a major effect and later confirmed to function as a hypomorphic mutation (Table 2.2) [41–43].
While often assumed that the reference strain (C57BL/6J) is wild type for the gene under investigation, it may actually be the abnormal gene in the reference strain. An example is alcohol dehydrogenase 7 (Adh7, formerly called Adh4, that is no longer listed in the Sanger SNP database). As shown in Table 2.3, there are two SNPs predicted to be missense mutations with significant effects [44]. However, the strains listed (129, C3H/HeJ, DBA/2J, and KK/HlJ) are actually wild type and the C57BL/6J (reference strain) and C57BL/6NJ are the hypomorphic mutant strains. This change partially explains alopecia and dermatitis that is a strain specific phenotype in most B6 substrains [45].
Table 2.2 SNP comparison between inbred strains for the Abcc6 gene. A search of the Sanger Mouse SNP database (17 January 2020) revealed a single base difference predicted to be a missense mutation (yellow) that has a predicted significant effect (*). Note that not all of the 129 substrains carry this allele.
| Gene | Chromosome | Position | dbSNP | Reference | 129P2/OlaHsd | 129S1/SvlmJ | 129S5SvEvBrd | C3H/HeJ | C57BL/6NJ | DBA/2J | KK/HiJ |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Abcc6 | 7 | 45,979,026 | rs32751584 | T | C | C | C | C | ‐ | C | C |
| Abcc6 | 7 | 45,979,027 | rs32751586 | G | ‐ | A | A | A | ‐ | A | A |
| Abcc6 | 7 | 45,979,329 | rs52492784 | T | C | C | C | C | ‐ | C | C |
| Abcc6 | 7 | 45,979,332 | rs255648560 | C | T | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ |
| Abcc6 | 7 | 45,979,342 | rs52081041 | T | C | C | C | C | ‐ | C | C |
| Abcc6 | 7 | 45,979,350 | rs52476049 | T | C | C | C | C | ‐ | C | C |
| Abcc6 | 7 | 45,979,428 | rs32751588 | T | C | C | C | C | ‐ | C | c |
| Abcc6 | 7 | 45,979,479 | rs226776926 | A | G | G | G | G | ‐ | G | G |
| Abcc6 | 7 | 45,979,481 | rs245254287 | T | C | C | C | C | ‐ | C | C |
| Abcc6 | 7 | 45,979,483 | rs215733716 | C | T | T | T | T | ‐ | T | T |
| Abcc6 | 7 | 45,979,503 | rs47309606 | A | G | G | G | G | ‐ | G | G |
| Abcc6 | 7 | 45,979,518 | rs32751593 | T | C | C | C | C | ‐ | C | C |
| Abcc6 | 7 | 45,979,519 | rs49208795 | G | T | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ |
| Abcc6 | 7 | 45,979,526 | rs50146914 | A | G | G | G | G | ‐ | G | G |
| Abcc6 | 7 | 45,979,719 | rs32752395 | C | ‐ | T* | T* | T* | ‐ | T* | T* |
| Abcc6 | 7 | 45,979,850 | ‐ | T | C | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ |
| Abcc6 | 7 | 45,980,046 | rs32752398 | C | T | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ |
| Abcc6 | 7 | 45,980,047 | rs32752399 | G | ‐ | A | A | A | ‐ | A | A |
| Abcc6 | 7 | 45,980,124 | rs32752401 | T | C | C | C | C | ‐ | C | C |
| Abcc6 | 7 | 45,980,195 | rs31113325 | C | T | T | T | T | ‐ | T | T |
| Abcc6 | 7 | 45,980,274 | rs216152409 | A | G | G | G | G | ‐ | G | G |
| Abcc6 | 7 | 45,980,412 | rs31560978 | C | T | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ |
| Abcc6 | 7 | 45,980,427 | rs32352446 | G | A | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ |
| Abcc6 | 7 | 45,980,475 | rs31369566 | A | G | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ |
| Abcc6 | 7 | 45,980,499 | rs49424268 | T | C | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ |
Table 2.3 Polymorphisms in Adh7. Two SNP in the Adh7 gene (formerly called Adh4) are predicted to be missense mutations (yellow) with a significant effect (*) in many inbred strains. However, actually this is only true for the reference strain (C57BL/6J) and the closely related substrain (C57BL/6NJ). Those predicted to have significant effects are in fact the wild type alleles.
| Gene | Chromosome | Position | dbSNP | Reference | 129P2/OlaHsd | 129S1/SvlmJ | 129S5SvEvBrd | C3H/HeJ | C57BL/6NJ | DBA/2J | KK/HiJ |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 0610031O16Rik | 3 | 138,221,632 | rs30512262 | G | C | C | C | C | ‐ | C | C |
| 0610031O16Rik | 3 | 138,222,187 | rs30594157 | T | C | C | C | C | ‐ | C | C |
| 0610031O16Rik | 3 | 138,223,190 | rs30907305 | G | A | A | A | A | ‐ | A | A |
| 0610031O16Rik | 3 | 138,223,276 | rs49048350 | A | T | T | T | T | ‐ | T | T |
| 0610031O16Rik | 3 | 138,223,314 | rs48657115 | T | G | G | G | G | ‐ | G | G |
| 0610031O16Rik | 3 | 138,223,345 | rs49621707 | A | T | T | T | T | ‐ | T | T |
| 0610031O16Rik | 3 | 138,223,449 | rs47855194 | C | T | T | T | T | ‐ | T | T |
| 0610031O16Rik | 3 | 138,223,512 | rs46440580 | T | C | C | C | C | ‐ | C | C |
| Adh7 | 3 | 138,223,922 | rs13468441 | C | T* | T* | T* | T* | ‐ | T* | T* |
| 0610031O16Rik | 3 | 138,224,573 | rs50005056 | C | T | T | T | T | ‐ | T | T |
| 0610031I16Rik | 3 | 138,224,578 | rs46271260 | A | G | G | G | G | ‐ | G | G |
| 0610031O16Rik | 3 | 138,225,390 | rs30170105 | T | C | C | C | C | ‐ | C | C |
| 0610031O16Rik | 3 | 138,225,871 | rs30695413 | G | A | A | A | ‐ | ‐ | A | A |
| 0610031O16Rik | 3 | 138,226,121 | rs31386034 | A | C | ~ | C | C | ‐ | ~ | ~ |
| 0610031O16Rik | 3 | 138,226,125 | rs31000950 | C | G | G | G | G | ‐ | G | G |
| 0610031O16Rik | 3 | 138,226,160 | rs30901573 | G | ‐ | ‐ | ‐ | A | ‐ | ‐ | ‐ |
| Adh7 | 3 | 138,226,410 | rs31091615 | A | G* | G* | G* | G* | ‐ | G* | G* |
| 0610031O16Rik | 3 | 138,228,417 | rs30262949 | T | C | C | C | C | ‐ | C | A |
| 0610031O16Rik | 3 | 138,228,503 | rs50248152 | G | A | A | A | A | ‐ | A | G |
| 0610031O16Rik | 3 | 138,228,653 | rs31428790 | A | G | G | G | G | ‐ | G | G |
| 0610031O16Rik | 3 | 138,228,722 | rs30904366 | A | G | G | G | G | ‐ | G | G |
| Adh7 | 3 | 138,231,370 | ‐ | T | g | ~ | ‐ | ||||
| Adh7 | 3 | 138,231,388 | rs50766077 | C | A | A | A | A | ‐ | A | A |
| Adh7 | 3 | 138,231,410 | rs46894990 | A | G | G | G | G | ‐ | G | G |
| Adh7 | 3 | 138,231,427 | rs46279078 | T | A | A | A | A | ‐ | A | A |
