Friday, February 20, 2015

NOD Mice Substrain Divergence - Runs of Homozygosity

Divergence or rather Differentiation (to use the right terminology), between natural ecotypes or subspecies has been studied in multiple pairs. The broad-scale patterns and underlying processes for such genome wide changes has been studied in detail

Do similar processes govern the "divergence" of  artificially inbred strains? Is Drift too strong for background selection to be relevant in such inbred lines? Data [Genetic Analysis of Substrain Divergence in NOD Mice] from a recent study of NOD mice sub-strains might provide some answers. While the study was restricted to sites fixed to homozygosity, it does provide some idea of the major regions that differ between the mouse strains. More detailed analysis of the mouse strains including multiple individuals might be necessary to understand if the diversity landscape of the genome has played any role in shaping the accumulation of genetic differences. 

The Supplementary table 4 provides a list of all the SNP's genotyped using the Mouse Diversity Array. We try to identify runs of homozygosity that share the same genealogy and note if these regions correspond to the deletions identified and validated in the study.



PositionVariants
ChrPos (mm10)Idd.regionSnpIdTypeBomTacMrkTacShiJclShiLtDvsShiLt
114207005JAX00242533G/CGGGCC
139035554Idd26JAX00002691T/-TT-TT
139035867Idd26JAX00247792C/-CC-CC
139035916Idd26JAX00002693A/-AA-AA
139057575Idd26JAX00002694C/-CC-CC
1111005763Idd5.4aJAX00262691A/-A-AAA
1111014417Idd5.4aJAX00262692T/-T-TTT
1111019979Idd5.4aJAX00262694G/-G-GGG
283392830JAX00494876G/---G-G
2131300866Idd13, Idd13-not B2mJAX00503778A/GAAAGA
38893755JAX00514596C/ACCCCA
324286919JAX00516977C/-CCC--
324320030JAX00516979T/-TTT--
324348995JAX00105316A/GAAA--
324383100JAX00516985T/-TTT--
333847305JAX00106024-/GGG-GG
333847927JAX00519037-/TTT-TT
333848126JAX00519038-/AAA-AA
333850816JAX00519044-/CCC-CC
333851250JAX00519045A/-AA-AA
333851593JAX00519046G/-GG-GG
365332947JAX00525208T/CTTTTC
444176075JAX00549396T/ATTTAA
495778743JAX00558533G/AGGGAG
522274118JAX00575925T/CTTTTC
541404231JAX00579937T/-T-TTT
566998537JAX00584961C/ACCCC-
573358239JAX00585757C/TCCCTT
638322613JAX00607572C/TCCCCT
653666162JAX00141075C/-TT-TT
661137631JAX00611572C/TCCCTT
97195978JAX00685032A/GAAAGG
929769301JAX00688769G/CGGGGC
9106903556JAX00704737G/AGGGGA
113243750JAX00023793G/AGGGAA
1239375537JAX00200149G/-G-GGG
13116909804Idd14JAX00371636G/AGGGGA
1532687601JAX00397403C/ACCCCA
1572708061JAX00405386G/AGGGGA
1629905094JAX00416944C/-CC-CC
1690657211JAX00427835G/AGGGAA
1858558824JAX00460581G/TGGGGT
1861847210JAX00461436G/AGGGGA
1866105915Idd21.2JAX00462793G/AGGGAA
1884871118Idd21.1JAX00467924-/TTT---
1950248464JAX00479604C/ACCCCA
X14217495JAX00177287C/ACCCAA
X101602508JAX00716621G/AGGGGA

In the above table the runs of fixed differences and what they are is listed below:


  1. First run (marked in blue) of fixed differences corresponds to the Idd26 locus.
  2. Next is the Idd5 locus. 
  3. The deletion on chromosome 3 spanning 24,272,052 and 24,383,100 has been validated by Sanger sequencing in this study.
  4. The second deletion on chromosome 3 spanning as many as 6 SNP's is located rather close to the first deletion.
The remaining clusters of 2 or 3 sites that share the same genealogy are probably too short to correspond to single events themselves. Nonetheless, it would be interesting to see if these fixed differences are localized to lower nucleotide diversity regions in the initial strains.

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