Deviations from Mendelian Inheritance on Bovine X-Chromosome Revealing Recombination, Sex-of-Offspring Effects and Fertility-Related Candidate Genes
Abstract
:1. Introduction
2. Materials and Methods
2.1. Genotype Data
2.2. Imputation
2.3. Male- and Female-Offspring Specific-TRD
2.4. Statistical Analyses
2.5. Pseudoautosomal Characterization
2.6. Functional Analyses
3. Results and Discussion
3.1. Characterization of X-Chromosome Using Parent-Offspring Genotyped Trios
3.2. Deviations from Mendelian Inheritance on the Pseudoautosomal Part of the Sex Chromosomes
3.3. Opposite Sire-TRD between Male- and Female-Offspring
3.4. Specific Sex-Offspring Sire-TRD
3.5. Deviations from Mendelian Inheritance on the Heterosomal Part of the X-Chromosome
3.5.1. SNP-by-SNP Analysis
3.5.2. Haplotype Analysis
3.6. Recessive TRD Pattern
3.7. Functional Impact around the Pseudoautosomal Boundaries Identified Using Opposite TRD Patterns between Male and Female Offspring
3.8. Enriched Metabolic Pathways, Diseases and Biological Functions Associated with the Positional Candidate Genes Displaying Deviations from Mendelian Inheritance on the X-Chromosome
3.9. Functional Candidate Genes Identified in the Candidate Regions with Deviations from Mendelian Expectations
3.10. Validation of Functional Candidate Genes Previously Identified in Independent Populations Using Genome-Wide Association Studies’ Meta-Analysis for Fertility Traits in Cattle
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Coordinates in Base Pairs | Frequency | Male-Offspring | Female-Offspring | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
n° Hetero 1 Sires | n° Hetero Dams | n° Info 2 Offspring | Sire-TRD (αs♂) | BF | n° Hetero Sires | n° Hetero Dams | n° Info Offspring | Sire-TRD (αs♀) | BF | ||
137,464,119 | 0.63 | 376 | 2307 | 10,297 | 0.02 | 0.79 | 275 | 1625 | 7100 | −0.04 | 104.2 |
138,080,118 | 0.46 | 699 | 4368 | 19,985 | −0.01 | 0.04 | 1281 | 20,752 | 48,445 | 0.03 | 1022.8 |
144,824,704 | 0.31 | 267 | 1691 | 8037 | 0.01 | 0.03 | 365 | 2258 | 8646 | 0.04 | 103.4 |
144,927,188 | 0.83 | 7 | 88 | 228 | 0.36 | 103.8 | 8 | 46 | 107 | −0.14 | 0.63 |
145,093,201 | 0.24 | 403 | 2284 | 10,759 | 0.00 | 0.02 | 361 | 1879 | 9007 | −0.04 | 104.2 |
145,322,565 | 0.67 | 280 | 1532 | 9045 | 0.02 | 1 | 364 | 1946 | 9432 | −0.08 | 1027.4 |
146,268,179 | 0.14 | 216 | 1351 | 6317 | −0.15 | 1058.9 | 334 | 5575 | 13,299 | −0.02 | 3.98 |
146,403,456 | 0.08 | 14 | 51 | 155 | −0.11 | 0.79 | 13 | 19 | 115 | 0.29 | 105.9 |
147,269,713 | 0.85 | 56 | 162 | 809 | 0.18 | 109.2 | 33 | 132 | 442 | 0.01 | 0.08 |
147,433,504 | 0.52 | 302 | 2111 | 10,749 | −0.07 | 1018.8 | 406 | 2793 | 11,668 | 0.02 | 0.63 |
147,587,823 | 0.58 | 98 | 290 | 1456 | 0.11 | 108.3 | 66 | 209 | 764 | −0.03 | 0.13 |
148,398,942 | 0.22 | 477 | 2871 | 14,803 | 0.02 | 10 | 851 | 14,732 | 37,427 | 0.05 | 1031.7 |
148,498,697 | 0.34 | 267 | 1685 | 8671 | −0.04 | 102.9 | 338 | 2173 | 8922 | 0.00 | 0.02 |
148,665,523 | 0.61 | 269 | 1853 | 8777 | 0.05 | 105.4 | 351 | 2335 | 8873 | −0.01 | 0.10 |
148,682,952 | 0.36 | 98 | 311 | 1556 | −0.11 | 108.8 | 67 | 225 | 795 | 0.03 | 0.13 |
Coordinates in Base Pairs | Offspring-Sex | n° Hetero 1 Dams | A × AB 2 | B × AB | Frequency M/(F) | TRD Parameters | ||||
---|---|---|---|---|---|---|---|---|---|---|
AA/A 3 | AB | B | A | AB | BB/B | |||||
4,134,094 | - | 391 | 111 | 46 | 88 | 209 | 150 | 623 | 0.15 (0.18) | αd = −0.12 (BF = 1013.3; ≤0.001 4) |
40,239,653 | - | 42,334 | 37,552 | 23,430 | 11,719 | 7816 | 15,685 | 22,229 | 0.64 (0.62) | αd = 0.02 (BF = 1020.6; ≤0.01) |
85,463,982 | - | 13,963 | 294 | 241 | 98 | 3401 | 9983 | 14,552 | 0.03 (0.04) | αd = −0.02 (BF = 109.2; ≤0.01) |
2,230,488 | M | 640 | 854 | 0 | 668 | 58 | 0 | 39 | 0.94 | αd♂ = 0.06 (BF = 104.14; ≤0.01) |
F | 477 | 632 | 628 | 0 | 0 | 20 | 18 | 0.93 | αd♀ = 0 (BF = 0.06; >5) | |
3,873,466 | M | 81 | 88 | 0 | 56 | 42 | 0 | 20 | 0.52 | αd♂ = 0.13 (BF = 107.2; ≤1) |
F | 48 | 35 | 25 | 0 | 0 | 19 | 32 | 0.49 | αd♀ = −0.01 (BF = 0.12; >5) | |
5,451,082 | M | 8389 | 10,984 | 0 | 10,371 | 1785 | 0 | 1673 | 0.86 | αd♂ = 0.01 (BF = 234.4; ≤0.01) |
F | 31,944 | 25,802 | 25,820 | 0 | 0 | 3570 | 3826 | 0.85 | αd♀ = 0 (BF = 0.01; >5) | |
22,030,046 | M | 1364 | 846 | 0 | 710 | 931 | 0 | 795 | 0.46 | αd♂ = 0.04 (BF = 103.2; ≤1) |
F | 1067 | 603 | 591 | 0 | 0 | 713 | 672 | 0.43 | αd♀ = 0.01 (BF = 0.04; >5) | |
65,136,071 | M | 12,977 | 5812 | 0 | 6482 | 13,607 | 0 | 14,685 | 0.34 | αd♂ = −0.02 (BF = 1014.3; ≤0.001) |
F | 49,960 | 13,780 | 14,055 | 0 | 0 | 32,898 | 33,032 | 0.37 | αd♀ = 0 (BF = 0.01; >5) | |
106,467,781 | M | 1627 | 425 | 0 | 513 | 1658 | 0 | 1943 | 0.21 | αd♂ = −0.04 (BF = 104.93; ≤1) |
F | 1128 | 305 | 309 | 0 | 0 | 1234 | 1265 | 0.21 | αd♀ = −0.01 (BF = 0.03; >5) | |
143,832,372 | M | 13,163 | 7425 | 0 | 7888 | 12,371 | 0 | 13,080 | 0.38 | αd♂ = −0.01 (BF = 104.78; ≤0.01) |
F | 52,914 | 19,253 | 18,869 | 0 | 0 | 30,256 | 30,222 | 0.44 | αd♀ = 0.0 (BF = 0.01; >5) | |
67,099,097 | M | 785 | 1192 | 0 | 1146 | 53 | 0 | 41 | 0.88 | αd♂ = 0.01 (BF = 0.05; >5) |
F | 504 | 936 | 586 | 0 | 0 | 28 | 37 | 0.91 | αd♀ = 0.11 (BF = 1014.5; ≤0.01) | |
125,033,467 | M | 767 | 1116 | 0 | 1082 | 56 | 0 | 41 | 0.95 | αd♂ = 0.01 (BF = 0.04; >5) |
F | 613 | 880 | 708 | 0 | 0 | 45 | 40 | 0.95 | αd♀ = 0.05 (BF = 363.1; ≤0.1) |
Coordinates in Base Pairs 1 | n° Hetero 2 Dams | Dam-TRD | BF | A × AB 3 | B × AB | Frequency % | ||||
---|---|---|---|---|---|---|---|---|---|---|
AA/A 4 | AB | B | A | AB | BB/B | |||||
134,602,363:135,936,247 4 | 10 | −0.49 | 1019.80 | 0 | 0 | 0 | 0 | 0 | 72 | 0.004 |
134,841,753:136,063,445 | 11 | −0.49 | 1019.80 | 0 | 0 | 0 | 0 | 0 | 72 | 0.004 |
134,624,675:135,970,186 | 10 | −0.49 | 1019.51 | 0 | 0 | 0 | 0 | 0 | 71 | 0.004 |
119,781,376:121,600,055 | 11 | −0.44 | 1019.13 | 0 | 0 | 0 | 1 | 4 | 91 | 0.007 |
123,894,981:125,905,926 | 101 | −0.22 | 1018.12 | 0 | 0 | 0 | 46 | 72 | 310 | 0.109 |
053,138,058:058,932,871 | 18 | −0.38 | 1016.11 | 0 | 0 | 0 | 3 | 10 | 103 | 0.021 |
056,821,723:059,606,508 | 12 | −0.47 | 1013.65 | 0 | 0 | 0 | 0 | 1 | 56 | 0.005 |
056,846,129:059,878,165 | 12 | −0.47 | 1013.65 | 0 | 0 | 0 | 0 | 1 | 56 | 0.005 |
129,911,571:132,268,728 | 15 | −0.44 | 1013.11 | 0 | 0 | 0 | 0 | 3 | 62 | 0.007 |
130,070,306:132,334,180 | 15 | −0.44 | 1013.11 | 0 | 0 | 0 | 0 | 3 | 62 | 0.007 |
130,112,536:132,620,448 | 15 | −0.44 | 1013.11 | 0 | 0 | 0 | 0 | 3 | 62 | 0.007 |
055,893,493:059,564,066 | 44 | −0.24 | 1012.55 | 0 | 0 | 0 | 31 | 40 | 199 | 0.058 |
129,070,088:131,766,182 | 12 | −0.45 | 1011.64 | 0 | 0 | 0 | 1 | 1 | 53 | 0.006 |
129,145,800:131,806,987 | 12 | −0.45 | 1011.64 | 0 | 0 | 0 | 1 | 1 | 53 | 0.006 |
129,193,110:131,960,783 | 12 | −0.45 | 1011.64 | 0 | 0 | 0 | 1 | 1 | 53 | 0.006 |
129,718,409:132,109,716 | 12 | −0.45 | 1011.64 | 0 | 0 | 0 | 1 | 1 | 53 | 0.006 |
129,887,133:132,211,189 | 12 | −0.45 | 1011.64 | 0 | 0 | 0 | 1 | 1 | 53 | 0.006 |
023,761,259:026,607,222 | 30 | −0.29 | 1011.07 | 0 | 0 | 0 | 5 | 25 | 118 | 0.025 |
056,962,509:060,125,574 | 13 | −0.40 | 1010.59 | 0 | 0 | 0 | 2 | 4 | 62 | 0.008 |
100,533,235:105,003,475 | 14 | −0.38 | 1010.47 | 0 | 0 | 0 | 5 | 3 | 67 | 0.011 |
Coordinates in Base Pairs (n. SNPs 1) | n° Hetero 2 Dams | AA × AB 3 | BB × AB | Frequency % | TRD Parameters | ||
---|---|---|---|---|---|---|---|
AA 4 | AB | AB | BB | ||||
307,557: 854,184 (10) | 247.00 | 2 | 8 | 300 | 281 | 0.40 | αg = −0.34 (BF = 103.35); δg = 0.21; (BF = 103.17) |
14,897,141:16,123,681 (10) | 452.00 | 1 | 8 | 559 | 579 | 0.60 | αg = −0.47 (BF = 1012.96); δg = 0.21; (BF = 106.64) |
23,895,384:27,387,980 (20) | 541.00 | 1 | 7 | 674 | 634 | 0.90 | αg = −0.40 (BF = 1012.08); δg = 0.24; (BF = 1010.46) |
30,116,443:30,459,667 (4) | 574.00 | 0 | 6 | 683 | 689 | 0.90 | αg = −0.51 (BF = 1019.6); δg = 0.25; (BF = 1011.37) |
48,750,092:52,808,614 (20) | 592.00 | 0 | 5 | 647 | 669 | 1.10 | αg = −0.50 (BF = 1017.26); δg = 0.23; (BF = 108.99) |
59,564,066:61,635,072 (20) | 525.00 | 0 | 8 | 550 | 549 | 1.80 | αg = −0.56 (BF = 1019.61); δg = 0.28; (BF = 1011.44) |
109,041,641:110,425,524 (20) | 438.00 | 1 | 8 | 513 | 539 | 1.20 | αg = −0.48 (BF = 1012.4); δg = 0.21; (BF = 105.82) |
127,431,846:129,887,133 (20) | 406.00 | 2 | 9 | 573 | 551 | 0.80 | αg = −0.37 (BF = 108.37); δg = 0.21; (BF = 106.78) |
p-Value | False Discovery Rate | Genes | |
---|---|---|---|
Canonical Metabolic Pathway | |||
Citrulline Degradation | 0.0072 | 0.603 | OTC |
Spermine Biosynthesis | 0.0145 | 0.603 | SMS |
PRPP Biosynthesis I | 0.0282 | 0.603 | PRPS1 |
Arginine Biosynthesis IV | 0.0427 | 0.603 | OTC |
Proline Biosynthesis II (from Arginine) | 0.0427 | 0.603 | OTC |
Urea Cycle | 0.0427 | 0.603 | OTC |
Pentose Phosphate Pathway (Non-oxidative Branch) | 0.0427 | 0.603 | TKTL1 |
Glycine Cleavage Complex | 0.0427 | 0.603 | GCSH |
Phosphatidylcholine Biosynthesis I | 0.0490 | 0.603 | PCYT1B |
Acetyl-CoA Biosynthesis I (Pyruvate Dehydrogenase Complex) | 0.0490 | 0.603 | PDHA1 |
Diseases and Functions | |||
X-linked hereditary disease | 3.21 × 10−47 | 1.6 × 10−44 | ADGRG2, ALG13, AMELX, AMER1, ANOS1, AP1S2, ARHGEF9, ARMCX5GPRASP2/GPRASP2, ARR3, BTK, CA5B, CDKL5, CNKSR2, COL4A6, FANCB, FGF13, FLNA, FRMD7, GLA, GPR143, HNRNPH2, IGSF1, KDM6A, KIF4A, MBTPS2, MECP2, MID2, mir221, NDUFA1, OPN1LW, OTC, PCDH19, PDHA1, PDK3, PHEX, PHKA2, PIGA, PIH1D3, PLP1, POLA1, PRPS1, RNF113A, RPS6KA3, RS1, SERPINA7, SMPX, SMS, SRPX2, TIMM8A, TSPAN7, UBE2A, ZC4H2, ZNF674 |
X-linked mental retardation | 1.47 × 10−15 | 3.7 × 10−13 | AP1S2, CNKSR2, HNRNPH2, KDM6A, KIF4A, MECP2, MID2, PDHA1, RNF113A, RPS6KA3, SMS, SRPX2, TSPAN7, UBE2A, ZC4H2, ZNF674 |
X-linked hearing loss | 1.29 × 10−8 | 2.2 × 10−6 | ARMCX5GPRASP2/GPRASP2, COL4A6, PRPS1, SMPX |
Syndromic X-linked mental retardation | 1.97 × 10−8 | 2.5 × 10−6 | AP1S2, CNKSR2, HNRNPH2, KDM6A, MECP2, SMS, SRPX2, UBE2A, ZC4H2 |
Familial mental retardation | 4.28 × 10−8 | 4.3 × 10−6 | AP1S2, CNKSR2, FLNA, HNRNPH2, KDM6A, KIF4A, MECP2, MID2, PDHA1, RNF113A, RPS6KA3, SMS, SRPX2, TSPAN7, UBE2A, ZC4H2, ZNF674 |
X-linked nonsyndromic sensorineural hearing loss | 1.46 × 10−6 | 1.2 × 10−4 | COL4A6, PRPS1, SMPX |
Autism or intellectual disability | 1.95 × 10−6 | 1.4 × 10−4 | AP1S2, CDKL5, CNKSR2, FLNA, HNRNPH2, KDM6A, KIF4A, MECP2, MID2, PDHA1, RNF113A, RPS6KA3, SMS, SRPX2, TSPAN7, UBE2A, ZC4H2, ZNF674 |
Familial syndromic intellectual disability | 2.57 × 10−6 | 1.6 × 10−4 | AP1S2, CNKSR2, FLNA, HNRNPH2, KDM6A, MECP2, SMS, SRPX2, UBE2A, ZC4H2 |
Childhood onset epilepsy syndrome | 3.63 × 10−6 | 2.0 × 10−4 | ARHGEF9, CDKL5, SRPX2 |
Cognitive impairment | 3.49 × 10−5 | 1.7 × 10−3 | AP1S2, ARHGEF9, CA5B, CNKSR2, FLNA, HNRNPH2, KDM6A, KIF4A, MECP2, MID2, PDHA1, RNF113A, RPS6KA3, SMS, SRPX2, TSPAN7, UBE2A, VEGFD, ZC4H2, ZNF674 |
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Id-Lahoucine, S.; Casellas, J.; Fonseca, P.A.S.; Suárez-Vega, A.; Schenkel, F.S.; Cánovas, A. Deviations from Mendelian Inheritance on Bovine X-Chromosome Revealing Recombination, Sex-of-Offspring Effects and Fertility-Related Candidate Genes. Genes 2022, 13, 2322. https://doi.org/10.3390/genes13122322
Id-Lahoucine S, Casellas J, Fonseca PAS, Suárez-Vega A, Schenkel FS, Cánovas A. Deviations from Mendelian Inheritance on Bovine X-Chromosome Revealing Recombination, Sex-of-Offspring Effects and Fertility-Related Candidate Genes. Genes. 2022; 13(12):2322. https://doi.org/10.3390/genes13122322
Chicago/Turabian StyleId-Lahoucine, Samir, Joaquim Casellas, Pablo A. S. Fonseca, Aroa Suárez-Vega, Flavio S. Schenkel, and Angela Cánovas. 2022. "Deviations from Mendelian Inheritance on Bovine X-Chromosome Revealing Recombination, Sex-of-Offspring Effects and Fertility-Related Candidate Genes" Genes 13, no. 12: 2322. https://doi.org/10.3390/genes13122322