Table 2 Gene set over-representation analysis of genes with deficit detected through a gene-based test of pLOFs (geneLOFs)

From: Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality

 

Expected homozygous count [1-5)

Expected homozygous count >=5

GENE SET

OBS/EXP < = 0.1

OBS/EXP > 0.1

P-valuea

OR [95%CI]a

OBS/EXP < = 0.1

OBS/EXP > 0.1

P-valuea

OR [95%CI]a

OMIM

AR OMIM

39 (39.4%)

103 (14.2%)

1.6 × 10−8

3.92 [2.42–6.32]

9 (47.4%)

147 (12.0%)

1.9 × 10−4

6.56 [2.32–18.3]

Other

60 (60.6%)

623 (85.8%)

  

10 (52.6%)

1074 (88.0%)

  

Total

99

726

—

—

19

1221

—

—

Human cell-line

Essential

31 (33.7%)

30 (4.7%)

1.5 × 10−14

10.2 [5.54–18.7]

11 (57.9%)

85 (8.3%)

9.1 × 10−8

15.1 [5.39–44.6]

Non-essential

61 (66.3%)

603 (95.3%)

  

8 (42.1%)

942 (91.7%)

  

Total

92

633

—

—

19

1027

—

—

KO mouse

Lethal or subviable

40 (57.1%)

104 (23.4%)

3.6 × 10−8

4.36 [2.51–7.64]

13 (86.7%)

179 (24.9%)

1.2 × 10−6

19.5 [4.35–179]

Viable

30 (42.9%)

341 (76.6%)

  

2 (13.3%)

539 (75.1%)

  

Total

70

445

—

—

15

718

—

—

  1. The analysis was performed using three different data sets: genes harboring variants reported to cause recessive Mendelian disease, genes essential for the growth of human cell lines identified through genome-wide screens, and orthologous mouse genes known to affect viability.
  2. GENE SET: number of geneLOFs with an expected homozygous count of (1,5] and >= 5 (see Supplementary Data 6 for details)
  3. OBS/EXP < = 0.1: deficit of homozygosity defined as a ratio of observed to expected homozygous count less than 0.1 among genes with an expected homozygous count over five; OBS/EXP > 0.1: ratio of observed to expected homozygous count over 0.1 among geneLOFs with expected homozygous count over five; EXP: number of homozygotes expected under HWE; OBS: number of homozygotes observed.
  4. OR [95%CI]: Odds-ratio [95% confidence interval].
  5. OMIM: AR OMIM: Gene linked to a mendelian disease linked with an autosomal recessive mode of inheritance in OMIM (see Supplementary Data 14 for details). Other: genes not known to harbor variants reported to cause recessive Mendelian disease.
  6. KO mouse: Homozygous knockout mouse mortality phenotypes (see Supplementary Data 16 for details). Lethal or subviable:  absence of live knockout (null) homozygote pups or fewer than 12.5% live knockout pups (half of the 25%). Viable: homozygous (null and wild type) and heterozygous pups are observed in the same or more than the expected normal Mendelian ratios.
  7. HUMAN CELL-LINE: Gene essentiality status for cell growth in human cell lines (DepMap). (see Supplementary Data 15 for details). Essential: If a gene’s inactivation significantly impairs a cell’s growth, it is categorized as an essential gene. Non-essential: When a gene’s inactivation does not significantly impair cell growth, it is considered a non-essential gene.
  8. aSignificance level based on the Fisher test.
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