Chow et al., 2015
Candidate genetic modifiers of retinitis pigmentosa identified by exploiting natural variation in Drosophila
[10.1093/hmg/ddv502]

Description

Eye size (area in pixels) was measured on F1 females from crosses of 173 DGRP males to a GMR-GAL4, UAS-Rh1^G69D strain, a Drosophila model of retinitis pigmentosa (smaller eyes are more degenerate). Eye size varied about twofold, and a GWAS found 106 candidate modifier genes.

Comments from curator

Phenotyping data comes from the Supplementary Material of the paper (journal page, also on PMC):
- Table S1 (ddv502supp_table1.xlsx): mean, median and standard deviation of the eye size of F1 females, for 173 DGRP crosses.
- Table S2 (ddv502supp_table2.xlsx): weight of the F1 females of 26 of these crosses.
- Table S3 (ddv502supp_table3.xlsx): eye size of F1 males, for 35 crosses.
Only these per-line values were published (no per-fly data), so the study has a summary dataset only.

These are F1 phenotypes, not phenotypes of the inbred DGRP lines: virgin females of a "donor" strain carrying GMR-GAL4 and UAS-Rh1^G69D recombined on chromosome 2 (derived from a single recombinant male, backcrossed for six generations to w¹¹¹⁸, kept over CyO) were crossed to males of each DGRP line. The F1 progeny express the misfolding rhodopsin mutant Rh1^G69D, a model of autosomal dominant retinitis pigmentosa, in the developing eye, so their eye size measures the severity of retinal degeneration in a heterozygous DGRP background (smaller eyes are more degenerate). Each value is assigned to the DGRP father line, as in the authors' GWAS, and the cross is given in the phenotype names (_xRh1G69D).

F1 flies were collected upon emergence, aged 3 days and flash frozen, and the left eye of each fly was imaged with a light microscope. Eye size is the area of the eye in pixels (ImageJ; the paper gives no conversion to µm²). At least 10 F1 females were measured per cross (room temperature, agar-dextrose-yeast food, 12:12 h light:dark). Males were measured only for some crosses, because many crosses had extensive male larval lethality. The line effect on female eye size was highly significant (ANOVA, P < 2.2 × 10^-16).

The summary dataset has:
- md_EyeArea_xRh1G69D: median eye area of the F1 females (Table S1), the phenotype of the authors' GWAS (GEMMA, 1,891,334 variants with MAF ≥ 0.05; the full results are in Table S4). It ranges from 14,264.5 pixels (DGRP_256) to 27,476 pixels (DGRP_239), as in the paper.
- mn_EyeArea_xRh1G69D and sd_EyeArea_xRh1G69D: mean and standard deviation of the eye area, for the females from Table S1 (173 lines) and for the males from Table S3 (35 lines).
- mn_Weight_xRh1G69D: weight of one F1 female (mg; mean of 10 flies weighed before eye imaging), for 26 lines (Table S2). It is not correlated with the median eye size: r = 0.094 (P = 0.65), which the paper reports as "r² = 0.09; P = 0.65".

Of note, Table S3 has errors:
- Its columns are labelled "median", but they hold means: the female values equal the Table S1 means for 33 of the 34 lines shared with Table S1, and most male values are not whole or half pixels. The male values are therefore uploaded as means (mn_), with sex M.
- Its female SD column is misaligned: for 18 of the 34 shared lines, the SD is the Table S1 SD of another line of the table (for example, RAL021 has the SD of RAL181). The female values of Table S3 are therefore not used (Table S1 has all of them). The male SDs are uploaded as published, but they cannot be checked and may be misaligned in the same way.
- DGRP_790: the female value of Table S3 (17,440.5) differs from its Table S1 mean (21,158.6). Table S1 is used.
- DGRP_272 is in Table S3 but not in Table S1 (it is not one of the 173 lines of the GWAS). Its male mean and SD are uploaded, but not its female value (19,535.9), since the female columns of Table S3 are unreliable.
The male and female columns of Table S3 correlate at r = 0.725 (35 lines, P = 8.6 × 10^-7), which the paper reports as "r² = 0.73".

Not uploaded: the RNAi knockdowns of the candidate genes crossed to the donor strain (Table S7; VDRC lines and their attP control, not DGRP lines), the GWAS results (Tables S4 and S5) and the GO enrichment (Table S6). The same eye sizes are reused by DGRPool study 112 (Palu et al. 2020) and study 117 (Amstutz et al. 2022), which were rejected for that reason.

174 DGRP lines 173 genotyped 1 not_genotyped

DGRP_021 DGRP_026 DGRP_038 DGRP_040 DGRP_042 DGRP_045 DGRP_049 DGRP_057 DGRP_059 DGRP_069 DGRP_073 DGRP_075 DGRP_083 DGRP_085 DGRP_088 DGRP_091 DGRP_093 DGRP_101 DGRP_105 DGRP_109 DGRP_129 DGRP_136 DGRP_138 DGRP_142 DGRP_149 DGRP_153 DGRP_158 DGRP_161 DGRP_176 DGRP_177 DGRP_181 DGRP_195 DGRP_208 DGRP_217 DGRP_223 DGRP_227 DGRP_228 DGRP_229 DGRP_233 DGRP_235 DGRP_237 DGRP_239 DGRP_256 DGRP_272 DGRP_280 DGRP_287 DGRP_301 DGRP_303 DGRP_304 DGRP_306 DGRP_307 DGRP_309 DGRP_310 DGRP_313 DGRP_315 DGRP_317 DGRP_318 DGRP_319 DGRP_320 DGRP_321 DGRP_324 DGRP_332 DGRP_335 DGRP_336 DGRP_338 DGRP_340 DGRP_350 DGRP_356 DGRP_357 DGRP_358 DGRP_359 DGRP_360 DGRP_361 DGRP_362 DGRP_365 DGRP_367 DGRP_370 DGRP_373 DGRP_374 DGRP_377 DGRP_379 DGRP_380 DGRP_381 DGRP_382 DGRP_383 DGRP_385 DGRP_386 DGRP_391 DGRP_392 DGRP_399 DGRP_405 DGRP_406 DGRP_409 DGRP_426 DGRP_427 DGRP_437 DGRP_439 DGRP_440 DGRP_441 DGRP_443 DGRP_461 DGRP_486 DGRP_491 DGRP_492 DGRP_502 DGRP_508 DGRP_513 DGRP_530 DGRP_531 DGRP_535 DGRP_555 DGRP_563 DGRP_584 DGRP_589 DGRP_595 DGRP_642 DGRP_646 DGRP_703 DGRP_705 DGRP_707 DGRP_712 DGRP_714 DGRP_716 DGRP_721 DGRP_727 DGRP_730 DGRP_732 DGRP_737 DGRP_738 DGRP_748 DGRP_761 DGRP_765 DGRP_774 DGRP_776 DGRP_783 DGRP_786 DGRP_787 DGRP_790 DGRP_796 DGRP_799 DGRP_801 DGRP_802 DGRP_804 DGRP_805 DGRP_808 DGRP_810 DGRP_812 DGRP_818 DGRP_819 DGRP_820 DGRP_821 DGRP_822 DGRP_832 DGRP_837 DGRP_843 DGRP_849 DGRP_850 DGRP_852 DGRP_853 DGRP_855 DGRP_859 DGRP_861 DGRP_879 DGRP_882 DGRP_884 DGRP_887 DGRP_890 DGRP_892 DGRP_894 DGRP_897 DGRP_900 DGRP_907 DGRP_908 DGRP_913

Datasets

Dataset	Phenotypes	DGRP lines
Summary dataset	4 phenotypes md_EyeArea_xRh1G69D mn_EyeArea_xRh1G69D mn_Weight_xRh1G69D sd_EyeArea_xRh1G69D	174 DGRP lines DGRP_021 DGRP_026 DGRP_038 DGRP_040 DGRP_042 DGRP_045 DGRP_049 DGRP_057 DGRP_059 DGRP_069 DGRP_073 DGRP_075 DGRP_083 DGRP_085 DGRP_088 DGRP_091 DGRP_093 DGRP_101 DGRP_105 DGRP_109 DGRP_129 DGRP_136 DGRP_138 DGRP_142 DGRP_149 DGRP_153 DGRP_158 DGRP_161 DGRP_176 DGRP_177 DGRP_181 DGRP_195 DGRP_208 DGRP_217 DGRP_223 DGRP_227 DGRP_228 DGRP_229 DGRP_233 DGRP_235 DGRP_237 DGRP_239 DGRP_256 DGRP_272 DGRP_280 DGRP_287 DGRP_301 DGRP_303 DGRP_304 DGRP_306 DGRP_307 DGRP_309 DGRP_310 DGRP_313 DGRP_315 DGRP_317 DGRP_318 DGRP_319 DGRP_320 DGRP_321 DGRP_324 DGRP_332 DGRP_335 DGRP_336 DGRP_338 DGRP_340 DGRP_350 DGRP_356 DGRP_357 DGRP_358 DGRP_359 DGRP_360 DGRP_361 DGRP_362 DGRP_365 DGRP_367 DGRP_370 DGRP_373 DGRP_374 DGRP_377 DGRP_379 DGRP_380 DGRP_381 DGRP_382 DGRP_383 DGRP_385 DGRP_386 DGRP_391 DGRP_392 DGRP_399 DGRP_405 DGRP_406 DGRP_409 DGRP_426 DGRP_427 DGRP_437 DGRP_439 DGRP_440 DGRP_441 DGRP_443 DGRP_461 DGRP_486 DGRP_491 DGRP_492 DGRP_502 DGRP_508 DGRP_513 DGRP_530 DGRP_531 DGRP_535 DGRP_555 DGRP_563 DGRP_584 DGRP_589 DGRP_595 DGRP_642 DGRP_646 DGRP_703 DGRP_705 DGRP_707 DGRP_712 DGRP_714 DGRP_716 DGRP_721 DGRP_727 DGRP_730 DGRP_732 DGRP_737 DGRP_738 DGRP_748 DGRP_761 DGRP_765 DGRP_774 DGRP_776 DGRP_783 DGRP_786 DGRP_787 DGRP_790 DGRP_796 DGRP_799 DGRP_801 DGRP_802 DGRP_804 DGRP_805 DGRP_808 DGRP_810 DGRP_812 DGRP_818 DGRP_819 DGRP_820 DGRP_821 DGRP_822 DGRP_832 DGRP_837 DGRP_843 DGRP_849 DGRP_850 DGRP_852 DGRP_853 DGRP_855 DGRP_859 DGRP_861 DGRP_879 DGRP_882 DGRP_884 DGRP_887 DGRP_890 DGRP_892 DGRP_894 DGRP_897 DGRP_900 DGRP_907 DGRP_908 DGRP_913	Download