DOI: 10.5061/dryad.x3ffbg7wp
title: Fine mapping highlights ITGAL and MUS81 loss-of-function mutations modulating recessive impacts in dairy cattle

description: We recently described several major-effect recessive loci impacting
 anatomical and lactation traits in dairy cattle. Two of these loci in
 particular presented multiple candidate causative variants, comprising
 tightly linked coding variants that could not be easily differentiated on
 a statistical or functional basis. Here, we re-examine the candidacy of
 these variants by leveraging a dataset of 1 million genotyped animals.
 Assessing lactation and bodyweight effects in conjunction with rare,
 recombined genotypes for the IL4R, KIAA0556, ITGAL, DPF2, and MUS81
 candidates, we highlight ITGAL and MUS81 as the most likely causative
 genes for the two QTL. Recombinant homozygotes for these genes present
 larger, more significant effects than other candidates at the same loci,
 with both representing premature stop mutations anticipated to inactivate
 ITGAL and MUS81. We further examined homozygotes for the ITGAL mutation to
 better understand the range of phenotypes impacted. While outwardly
 normal, ITGAL mutants showed significant differences in the number and
 composition of circulating leukocytes, consistent with the role of ITGAL
 as a key mediator of leukocyte signalling, adhesion, and migration. These
 results demonstrate how near-perfectly linked candidate mutations can be
 differentiated given population-scale data, and highlight the ITGAL and
 MUS81 mutations as diagnostic targets to help manage the frequency of
 these variants.
description: The full methods can be found in the Supplementary Methods and
 Materials in the final published article, which is Open Access: https://doi.org/10.1111/age.70027
description: # Fine mapping highlights ITGAL and MUS81 loss-of-function mutations
 modulating recessive impacts in dairy cattle Full author list: [Laura
 Duntsch](https://onlinelibrary.wiley.com/authored-by/Duntsch/Laura), [Swati Jivanji](https://onlinelibrary.wiley.com/authored-by/Jivanji/Swati), [Thomas Lopdell](https://onlinelibrary.wiley.com/authored-by/Lopdell/Thomas), [Edwardo G. M. Reynolds](https://onlinelibrary.wiley.com/authored-by/Reynolds/Edwardo+G.+M.), [Liam Williams](https://onlinelibrary.wiley.com/authored-by/Williams/Liam), [Mathew D. Littlejohn](https://onlinelibrary.wiley.com/authored-by/Littlejohn/Mathew+D.) [https://doi.org/10.1111/age.70027](https://doi.org/10.1111/age.70027) ## Description of the data and file structure Contact Information Name: Laura Duntsch Institution: Livestock Improvement Corporation, New Zealand Email: laura.duntsch@lic.co.nz ### Dataset Overview This dataset contains the data required to replicate analyses in Duntsch et al. #### Funding The research was financially supported by the Ministry of Business, Innovation and Employment (MBIE; Wellington, New Zealand) and the Ministry of Primary Industries (MPI; Wellington, New Zealand), who independently co-funded the work through the Endeavour Fund (LICX1802) and (now historical) Primary Growth Partnership research programmes, respectively. Funders had no role in the analysis or interpretation of the data, or in writing the manuscript. #### Ethics Approval The majority of genotype and phenotype data were generated as part of routine commercial activities outside the scope of that requiring formal committee assessment (as defined by the above guidelines). ### Files and variables #### File: chr25_lactation.csv **Description:**  ##### Variables * Identifier: Anonymized animal * chr25:24904939: Genotype for this position (Bos taurus, ARS 1.2) * chr25:25161613: Genotype for this position (Bos taurus, ARS 1.2) * chr25:26689392: Genotype for this position (Bos taurus, ARS 1.2) * Fat: Adjusted phenotype describing fat yield deviation * Protein: Adjusted phenotype describing protein yield deviation * Volume: Adjusted phenotype describing milk volume deviation * PC1 - PC15: Principal components #### File: chr29_lactation.csv **Description:**  ##### Variables * Identifier: Anonymized animal * chr29:43546966: Genotype for this position (Bos taurus, ARS 1.2) * chr29:43979681: Genotype for this position (Bos taurus, ARS 1.2) * Fat: Adjusted phenotype describing fat yield deviation * Protein: Adjusted phenotype describing protein yield deviation * Volume: Adjusted phenotype describing milk volume deviation * PC1 - PC15: Principal components #### File: chr29_bodyweight.csv **Description:** Data for linear model testing genotype effect on bodyweight; as loaded into in R ##### Variables * Identifier: Anonymized animal * chr29:43546966: Genotype for this position (Bos taurus, ARS 1.2) * chr29:43979681: Genotype for this position (Bos taurus, ARS 1.2) * Bodyweight: Adjusted phenotype describing juvenile bodyweight * PC1 - PC15: Principal components ## Code/software R (v4.2.1): lm() function of *stats* package