Population dynamics of potentially harmful haplotypes: a pedigree analysis

Abstract

Background: The identification of low-frequency haplotypes, never observed in homozygous state in a population, is considered informative on the presence of potentially harmful alleles (candidate alleles), putatively involved in inbreeding depression. Although identification of candidate alleles is challenging, studies analyzing the dynamics of potentially harmful alleles are lacking. A pedigree of the highly endangered Gochu Asturcelta pig breed, including 471 individuals belonging to 51 different families with at least 5 offspring each, was genotyped using the Axiom PigHDv1 Array (658,692 SNPs). Analyses were carried out on four different cohorts defined according to pedigree depth and at the whole population (WP) level.

Results: The 4,470 Linkage Blocks (LB) identified in the Base Population (10 individuals), gathered a total of 16,981 alleles in the WP. Up to 5,466 (32%) haplotypes were statistically considered candidate alleles, 3,995 of them (73%) having one copy only. The number of alleles and candidate alleles varied across cohorts according to sample size. Up to 4,610 of the alleles identified in the WP (27% of the total) were present in one cohort only. Parentage analysis identified a total of 67,742 parent-offspring incompatibilities. The number of mismatches varied according to family size. Parent-offspring inconsistencies were identified in 98.2% of the candidate alleles and 100% of the LB in which they were located. Segregation analyses informed that most potential candidate alleles appeared de novo in the pedigree. Only 17 candidate alleles were identified in the boar, sow, and paternal and maternal grandparents and were considered segregants.

Conclusions: Our results suggest that neither mutation nor recombination are the major forces causing the apparition of candidate alleles. Their occurrence is more likely caused by Allele-Drop-In events due to SNP calling errors. New alleles appear when wrongly called SNPs are used to construct haplotypes. The presence of candidate alleles in either parents or grandparents of the carrier individuals does not ensure that they are true alleles. Minimum Allele Frequency thresholds may remove informative alleles. Only fully segregant candidate alleles should be considered potentially harmful alleles. A set of 16 candidate genes, potentially involved in inbreeding depression, is described.

Keywords: Allele-Drop-In events; Linkage blocks; Pedigree variation; Population genomics; Potentially harmful alleles.

Fig. 1

Allelic frequencies per cohort defined according to pedigree depth (BP, G12, G23 and G3), and in the whole typed population. Plot illustrates the total number of alleles identified (in blue), the number of candidate alleles (in orange), and the number of alleles that are identified in one cohort only (in grey). The number of individuals typed in each of the cohorts and in the whole population are in brackets

Fig. 2

Pedigrees showing the segregation of six non-candidate alleles in the Gochu Asturcelta population analyzed. Boars are in squares and sows are in circles. Black squares and circles identify the carrier individuals. Plots A and B show the pedigree of sow 343 for alleles 104 on LB196 and 109 on LB1656, respectively. Plots C and D show the pedigree of boar 486 for alleles 112 on LB2925 and 109 on LB3315, respectively. Plot E shows the pedigree of sow 332 for allele 111 on LB645; and Plot F shows the pedigree of sow 167 (mated with two different boars) for allele 106 on LB3194. Only carrier offspring are included

Fig. 3

Dispersion plots constructed according to family size (on the Y-axis) and the total number of parents-offspring inconsistencies per family (on the X-axis; Plot A) and the mean number of parents-offspring inconsistencies per family (on the X-axis; Plot B)

Fig. 4

Venn diagrams summarizing the relationships between the 5,466 candidate alleles identified in the whole population and the 3,405 alleles involved in parents-offspring incompatibilities (Plot A). The relationships between the 3,405 LB on which parent-offspring allelic incompatibilities were identified and the 2,031 LB carrying candidate (potentially harmful) haplotypes at the whole population level are also summarized (Plot B)

Fig. 5

Pedigrees showing the segregation of four candidate alleles in the Gochu Asturcelta population analyzed. Boars are in squares and sows are in circles. Black squares and circles identify the carrier individuals. Plot A shows the fully segregant allele 101 on LB3529 which is transmitted from the founder boar 20 to the daughter 67 and five grandsons. Plots B (allele 102 on LB746), C (allele 105 on LB2481), and D (allele 103 on LB706) show pedigrees in which candidate alleles could be considered as identified de novo except for their identification in grandparents or great-grandparents

Fig. 6

Venn diagram illustrating the frequency in which the 5,466 candidate alleles identified in the whole population could be identified in the fathers, the mothers, the paternal grandfathers, or the maternal grandfathers of the carrier

Fig. 7

Pedigree illustrating the segregation of 17 segregant candidate alleles in the Gochu Asturcelta population analyzed. Boars are in squares and sows are in circles. Open squares and circles identify the non-carrier individuals. Letters beside the identification of the individuals mean that the individual carries segregant candidate haplotypes in the following LB (allele code in brackets): (A) LB1260 (101), LB1271 (101), LB3444 (103), LB3445 (106), LB3446 (106), LB3448 (104), LB3449 (104), LB3450 (103), LB3452 (104), LB3453 (103), LB3495 (101), LB3515 (101), LB3525 (101), LB3526 (101), LB3529 (101); (B) LB3444 (103), LB3445 (106), LB3446 (106), LB3448 (104), LB3449 (104), LB3450 (103), LB3452 (104), LB3453 (103), LB3495 (101), LB3515 (101), LB3525 (101), LB3526 (101), LB3529 (101); (C) LB3444 (103), LB3446 (106), LB3448 (104), LB3449 (104), LB3450 (103), LB3452 (104), LB3453 (103), LB3495 (101), LB3515 (101), LB3525 (101), LB3526 (101), LB3529 (101); (D) LB1260 (101), LB1271 (101), LB3495 (101), LB3515 (101), LB3525 (101), LB3526 (101), LB3529 (101); (E) LB1260 (101), LB1271 (101), LB1781 (103), LB1788 (103); (F) LB3525 (101), LB3526 (101), LB3529 (101); (G) LB1260 (101), LB1271 (101); (H) LB1781 (103), LB1788 (103); (I) LB1788 (103); and (J) LB1271 (101). Individuals carrying the same haplotypic combination are in the same color