Indirect molecular diagnosis of copper toxicosis in Bedlington terriers is complicated by haplotype diversity

Positional cloning recently identified the mutation causing copper toxicosis (CT) in Bedlington terriers. Isolation of the MURR1 gene will be of great value in developing a reliable diagnostic test for the breeding of a copper toxicosis-free stock. It will replace the current diagnostic test using the CT-linked marker, C04107, which is located in intron 1 of the MURR1 gene with a distance of approximately 8 kb from the exon 2 deletion. Despite the short distance between C04107 and the CT mutation, possible recombinant dogs have been reported with C04107. Although these dogs have a normal phenotype, they carry the C04107 allele 2, which is associated with CT. To study the origin of this possible recombination event we collected a pedigree consisting of two unaffected American Bedlington terriers and their litter of four pups, which were all homozygous for the C04107 2,2 genotype. Mutation analysis showed that two dogs were heterozygous for the CT exon 2 deletion mutation, whereas four dogs were homozygous for the wild-type (WT) allele. Haplotype analysis was performed using two DNA markers in the MURR1 gene and four DNA markers flanking the gene and spanning a region of approximately 600 kb. Surprisingly, we identified a new haplotype (haplotype C) that contains allele 2 of marker C04107 in combination with the WT MURR1 allele. Analysis of the flanking markers suggests there are different genetic backgrounds in the Bedlington terrier population.     

Diagnostic value of a microsatellite DNA marker for copper toxicosis in West-European Bedlington terriers and incidence of the disease

Recently, linkage of a DNA microsatellite marker to inherited copper toxicosis has been reported in American Bedlington terrier families. Due to the fact that there is little exchange of breeding stock between the USA and Europe, it remains to be investigated whether in Europe the marker is informative and is linked with the disease. We have therefore examined the diagnostic value of the microsatellite marker in the European Bedlington. In 130 dogs at least one year of age (62 from The Netherlands, 35 from Belgium, and 33 from Germany) histo- or cytochemical staining of copper was done in liver biopsies. Based on liver histo- or cytochemistry, 51 dogs were obligate carriers, and 25 dogs had copper toxicosis. The inferred genotypes of these 76 dogs were compared with the marker genotypes. All dogs with the disease were homozygous for the 167 bp marker allele. All obligate carriers were heterozygotes with the 167 bp and a 163-bp alleles. All phenotypically healthy dogs were either homozygous for the 163 bp allele or heterozygous. Thus, the marker was in complete linkage disequilibrium with the putative copper toxicosis gene with the 167 bp allele in phase with the disease allele. The frequencies of the 167 bp and the 163 bp allele, respectively, were 0.33 and 0.67 in Dutch dogs, 0.31 and 0.69 in German dogs, and 0.57 and 0.43 in Belgian dogs. We have confirmed the utility of this marker for diagnosis of inherited copper toxicosis in European Bedlington terriers.     

Characterization of the COMMD1 (MURR1) mutation causing copper toxicosis in Bedlington terriers

Copper toxicosis is an autosomal recessive disorder affecting Bedlington terriers, characterized by elevated liver copper levels and early death of affected dogs. Genetic linkage mapping studies initially identified linkage between the disease and the microsatellite marker C04107. Subsequently, the deletion of exon 2 of the copper metabolism domain containing 1 (COMMD1) gene (formerly MURR1) was shown to be the major cause of copper toxicosis, although the deletion breakpoints were not defined. In this investigation, polymerase chain reaction (PCR)-based techniques and sequencing were used to isolate the deletion breakpoints, utilizing the newly available dog genome sequence. The breakpoints were positioned at 65.3091 and 65.3489 Mb of dog chromosome 10, in intron 1 and intron 2 of COMMD1 respectively, a deletion of 39.7 kb. The two breakpoints share sequence homology suggesting that homologous recombination may have been responsible for the deletion. Using this information, a genomic diagnostic test for the COMMD1 deletion was developed and compared with microsatellite C04107 genotypes of 40 Bedlington terriers. Results from the 40 samples showed allele 2 of C04107 to be in linkage disequilibrium with the COMMD1 deletion.     

New haplotypes in the Bedlington terrier indicate complexity in copper toxicosis

Copper toxicosis (CT) is an autosomal recessive disorder common in Bedlington terriers. Previously, the CT locus was mapped to canine Chromosome (Chr) 10q26 through linkage to marker C04107. Diagnosis, traditionally based on liver biopsy, has recently shifted to interpretation of the C04107 microsatellite alleles where allele 2 segregates with the disease with 90–95% accuracy. Recently, CT has been attributed to a deletion of exon 2 in the MURR1 gene. We also identified a deletion of exon 2 of MURR1 in our collection of 2-2 homozygous affected terriers. However, our collection also included affected 1-1 homozygotes and 1-2 heterozygotes, and these dogs did not have the homozygous deletion. In addition to C04107, we analyzed an adjacent microsatellite (C04107B), and two novel SNPs, all within intron 1 of MURR1, and sequenced all exons and their intronic boundaries. Pedigree analysis indicates that there are two typical haplotypes, one normal and one affected, maintaining complete linkage disequilibrium between C04107 allele 2 and the deletion in most pedigrees. Most importantly, we identified a recombinant haplotype present in a North American pedigree, where allele 2 is not linked with the deletion, and a fourth haplotype containing a splice site variant. Although the splice site alteration appears to be a normal variant, it is present in two affected dogs, which do not carry homozygous deletions of MURR1.     

Copper toxicosis in non-COMMD1 Bedlington terriers is associated with metal transport gene ABCA12

Wilson’s disease, caused by a mutation in the ATP-ase 7B gene, is the only genetically characterised human disease with inhibition of biliary copper excretion and toxic copper accumulation in liver and occasionally brain. A similar copper toxicosis occurs in Bedlington terriers (CT) with liver damage only. Although CT has been associated with a defect in the COMMD1 gene (COMMD1 ^del/del), Bedlington terriers with CT and lacking this mutation are also recognised (non-COMMD1 ^del/del).A study was designed to identify any other gene polymorphisms associated with copper toxicity in Bedlington terriers employing genome wide association studies (GWAS) followed by deep sequencing of the candidate region. Blood for DNA analysis and liver for confirmation of the diagnosis was obtained from 30 non-COMMD1 ^del/del Bedlington terriers comprising equal numbers of CT-affected dogs and controls. DNA was initially subjected to GWAS screening and then further sequencing to target the putative mutant gene.The study has identified a significant disease association with a region on chromosome 37 containing identified SNP’s which are highly significantly associated with non-COMMD1 ^del/del Bedlington terrier CT. This region contains the ABCA12 gene which bears a close functional relationship to ATP-ase 7B responsible for Wilson’s disease in man.     

Assessment of the population structure of five Finnish dog breeds with microsatellites

Genetic variabilities within and between Finnish populations of Golden Retrievers, German Shepherds, Wirehaired Dachshunds, Pembroke Welsh Corgis and Bedlington Terriers were quantified with microsatellite allele numbers, observed heterozygosities, expected heterozygosities, FIS estimates, FST estimates and DS distances. In a sample of 50 individuals from each, breed and ten polymorphic loci, the highest genetic diversity was exhibited in the Wirehaired Dachshunds and lowest in the Bedlington Terriers. Although statistically significant deviations from the Hardy-Weinberg (H-W) equilibrium were observed, they occurred at an unexpectedly low frequency. Most strikingly, the extremely small Bedlington Terrier population displayed genotypes in H-W proportions in all investigated loci. The H-W deviations always occurred with positive FIS estimates, which, on average, were not larger than values reported for free-living canids. Genetic differentiation between the breeds was very large. As a comparison, present estimates were, on average, over two times higher than previously observed between breeds of sheep, and over two times higher than the highest estimates reported between human populations. Moreover, the highest DS distances were only slightly lower than the lowest values inferred between humans and chimpanzees. Severe bottlenecks in the recent past of the examined breeds were not statistically supported. The presented data imply genetic isolation and intense artificial selection in the history of these breeds of dogs.     

Inherited copper toxicosis with emphasis on copper toxicosis in Bedlington terriers

Canine copper toxicosis is an important inherited disease in Bedlington terriers, because of its high prevalence rate and similarity to human copper storage disease. It can lead to chronic liver disease and occasional haemolytic anaemia due to impaired copper excretion. The responsible gene for copper toxicosis in Bedlington terriers has been recently identified and was found not to be related to human Wilson’s disease gene ATP7B. Although our understanding of copper metabolism in mammals has improved through genetic molecular technology, the diversity of gene mutation related to copper metabolism in animals will help identify the responsible genes for non-Wilsonian copper toxicoses in human. This review paper discusses our knowledge of normal copper metabolism and the pathogenesis, molecular genetics and current research into copper toxicosis in Bedlington terriers, other animals and humans.     

Evaluation of genetic differentiation in Bos indicus cattle breeds from Marathwada region of India using microsatellite polymorphism

Elucidation of genetic variability and genetic relationship among breeds has direct relevance with the issues of sustainable use of domestic animal genetic resources. In the present study, genetic polymorphism was evaluated using 22 microsatellite loci in unrelated samples of Red Kandhari and Deoni cattle breeds inhabiting the same geographical area of Marathwada region in Maharashtra state (western India). This work was mainly aimed at assessing the current genetic diversity to understand whether the two zebu populations in question are genetically differentiated. A total of 164 alleles were detected with an average of 5.82 and 5.86 alleles per locus (MNA) in Red Kandhari and Deoni breeds, respectively. The estimated mean observed (Ho) and expected (He) heterozygosity were 0.47 and 0.64 in Red Kandhari vs. 0.57 and 0.69 in Deoni cattle, respectively, demonstrating considerable level of genetic variation in both the populations. Mean estimates of F statistics were: F (FIT) = 0.315 +/- 0.035, f(FIS) = 0.231 +/- 0.031, theta(FST) = 0.110 +/- 0.022, with both the breeds exhibiting significant deficit of heterozygotes (FIS = 0.179 in Deoni; 0.278 in Red Kandhari). The multilocus FST values implied that 11.0% of the total genetic variation corresponds to breed and were statistically greater than zero for the two populations, suggesting population division. The evaluation of exact test also indicated that allele frequencies across all the loci differed significantly (P < 0.001) between two zebu breeds, further supporting population differentiation. Different genetic distance measures showed considerable levels of distances between the two cattle breeds (0.318 = Nei's standard DS; 0.250 = Nei's DA; 0.416 = Cavalli-Sforza and Edwards's Dc; 0.164 = Reynold's, and 2.64 = Delta mu square (dmicro)2. Bayesian statistical approach to assign each individual to the population also supported considerable differentiation between the two cattle breeds, possibly reflecting the limited gene flow between the two Marthwada cattle populations. The existence of cohesive breeding structure of both the breeds was further substantiated by allele-sharing distance measures (DAS) among individual animals. The results of this study thus revealed that the two Bos indicus breeds sharing the common breeding tracts are genetically differentiated enough as separate breeds.     

Association between population structure and allele frequencies of the glycogen synthase 1 mutation in the Austrian Noriker draft horse

The aim of this study was to determine the allele frequency of the glycogen synthase 1 (GYS1) mutation associated with polysaccharide storage myopathy type 1 in the Austrian Noriker horse. Furthermore, we examined the influence of population substructures on the allele distribution. The study was based upon a comprehensive population sample (208 breeding stallions and 309 mares) and a complete cohort of unselected offspring from the year 2014 (1553 foals). The mean proportion of GYS1 carrier animals in the foal cohort was 33%, ranging from 15% to 50% according to population substructures based on coat colours. In 517 mature breeding horses the mutation carrier frequency reached 34%, ranging on a wider scale from 4% to 62% within genetic substructures. We could show that the occurrence of the mutated GYS1 allele is influenced by coat colour; genetic bottlenecks; and assortative, rotating and random mating strategies. Highest GYS1 carrier frequencies were observed in the chestnut sample comprising 50% in foals, 54% in mares and 62% in breeding stallions. The mean inbreeding of homozygous carrier animals reached 4.10%, whereas non‐carrier horses were characterized by an inbreeding coefficient of 3.48%. Lowest GYS1 carrier frequencies were observed in the leopard spotted Noriker subpopulation. Here the mean carrier frequency reached 15% in foals, 17% in mares and 4% in stallions and inbreeding decreased from 3.28% in homozygous non‐carrier horses to 2.70% in heterozygous horses and 0.94% in homozygous carriers. This study illustrates that lineage breeding and specified mating strategies result in genetic substructures, which affect the frequencies of the GYS1 gene mutation.     

Inheritance of self-compatibility in almond: breeding strategies to assure self-compatibility in the progeny

To assure self-compatibility in the progenies, three different crosses were conducted for the first time in an almond breeding programme: self-pollination (266 descendants from 30 families), crosses between parents sharing an S-allele (108 descendants from five families) and crosses with homozygous self-compatible parents (62 descendants from five families). Depending on the cross, self-compatibility in the progenies was determined by observing pollen tube growth (by means of fluorescence microscopy), stylar S-RNases analysis or allele-specific PCR. The results obtained fit with the accepted hypothesis of inheritance of self-compatibility and the three crossing strategies used ensured 100% of self-compatible descendants. These strategies increase the efficiency of the breeding programme and avoid the laborious task of evaluating this characteristic. From the breeding point of view, self-fertilisation and crosses between relatives tend to produce inbreeding. Furthermore, these methods reduce the possibilities of choosing the parental combination. The use of homozygous self-compatible parents does not have any of these disadvantages. As far as we know, this is the first time that allele-specific PCR has been used for early selection of self-compatible seedlings. The advantages and disadvantages of the three methodologies used to determine self-compatibility are discussed.     

神农架川金丝猴人工补食群的遗传多样性和亲缘关系

以湖北神农架国家级自然保护区的川金丝猴人工补食群体为研究对象,利用微卫星遗传标记对该群体的遗传多样性和亲缘关系进行研究,并对其种群的遗传多样性发展趋势进行了预测。结果显示,12个微卫星位点在该补食群体中共检测到50个等位基因,平均观察杂合度和平均期望杂合度分别为0.668和0.630,多态信息含量为0.442-0.696,平均0.567。亲权鉴定中共鉴定出11个父-母-子单元,各单元未有近亲繁殖的状况。亲缘系数结果显示具有亲缘关系的个体对达21.64%,群体平均亲缘系数为0.1108,现6个家庭单元中有两对候选亲本具有亲缘关系,表明该群体存在较高的近交风险。遗传多样性变化趋势的模拟结果表明,种群的数量对遗传多样性的影响比较大,群体中雄雌比例也对遗传多样性的损失有影响;为避免近亲交配,保持群体的遗传多样性水平,建议进一步做好人工补食群金丝猴的个体识别,完善家庭系谱,明确繁殖个体的遗传背景;引入一批有效的建群者来增加种群的数量及优化雄雌的比例。     

A study of the role of metallothionein in the inherited copper toxicosis of dogs.

The role of metallothionein (MT) was assessed in the copper-loading disease prevalent in Bedlington terriers. Fractionation of tissue supernatants over Sephadex G-75 showed that most of the additional cytosolic copper present in liver tissue of these dogs was bound to MT, and that substantially more MT-bound copper could be solubilized by detergent plus mercaptoethanol. Zinc contents were only slightly raised, although most of the extra zinc was associated with a 4000-Mr ligand. Ion-exchange chromatography revealed two isoproteins, MT1 and MT2, in all the dog liver samples examined. In Bedlington terrier liver, copper associated with both isoproteins was increased, although the increase for MT2 was greater than for MT1. The content of MT protein was also raised, although cell-free translations and RNA blots of total liver RNA showed that this increase was not associated with a rise in MT mRNA. The significance of these results to the mechanism of copper accumulation in the Bedlington terrier disorder is discussed.     

湖北野生春兰资源遗传多样性的ISSR分析

近年来,由于过度采挖和生境片断化,湖北野生春兰(Cymbidiumgoeringii)资源正面临着灭绝的危险。本文采用ISSR分子标记技术对湖北省内的11个春兰野生居群共325个个体的遗传多样性水平及居群遗传结构进行了研究。11个引物共检测到127个位点,其中112个为多态位点,占88.19%。POPGENE分析结果表明:与其他兰科植物相比,春兰具有丰富的遗传变异(在物种水平上,He=0.2628,Ho=0.4037;在居群水平上,PPL=63.06%,He=0.1945,Ho=0.2958)。Nei's遗传多样性分析和AMOVA分析表明,各居群间产生了一定程度的遗传分化(GST=0.2440,FST=0.2207)。居群间一定程度的遗传分化可能是由生境破坏和基因流障碍(Nm=0.8828)引起。UPGMA聚类分析可知,与其他居群相比,恩施地区的5个居群,即巴东(BD)、福宝山(FBS)、宣恩(XE)、毛坝(MB)、来凤(LF)优先聚成一支,而大悟(DW)居群单独聚为一支。同时本研究也表明,虽然春兰自交亲和,但在自然界中其繁育系统还是以异交为主。鉴于春兰资源的遗传多样性现状和其相应的居群遗传结构,我们建议在遗传多样性较高的来凤(LF)、京山(JS)、大悟(DW)居群设立保护点进行就地保护;而对资源破坏最为严重的毛坝(MB)和宣恩(XE)居群要实行迁地保护。     

种群微卫星DNA分析中样本量对各种遗传多样性度量指标的影响

我们以中国飞蝗种群的微卫星遗传分析数据为例 ,评估了取样对种群遗传多样性指标的影响 ,结果显示 :样本大小与所观测到的每位点等位基因数、平均等位基因数及基因丰富度指数均呈显著正相关 ,而与期望杂合度无显著相关 ;微卫星位点多态性的高低直接影响所观测到的种群基因丰富度及其检测所需的样本量 ;对大多数种群遗传和分子生态学研究而言 ,30 - 5 0个个体是微卫星DNA分析所需要的最小样本量。基因丰富度经过稀疏法或多次随机抽样法校正后 ,可适用于瓶颈效应等种群历史数量变动的检测。另外 ,在研究中 ,还应避免采集时间的不同及样本的性比构成所可能造成的对种群遗传结构的影响     

微卫星DNA标记探讨镜鲤的种群结构与遗传变异

采用30个微卫星分子标记, 对5个镜鲤群体的观测杂合度(^H_o)、期望杂合度(^H_e)、多态信息含量(PIC)和有效等位基因数(^A_e)等进行了遗传检测, 根据基因频率计算遗传相似系数和Nei氏标准遗传距离, 以c2检验估计Hardy-Weinberg平衡, 以近交系数(FST)和基因流(Nm)分析群体的遗传分化。同时, 使用PHYLIP3.63软件绘制基于Nei氏标准遗传距离的UPGMA聚类图, 并进行bootstrap自举检验验证进化树的可靠性。在德国镜鲤选育系(Scattered Cyprinus carpio L.)和来自4个不同养殖场(松浦、东岗、奉城和辽中)的德国镜鲤群体中共检测到7 083个扩增片段, 长度在102 ~ 446 bp之间, 在群体内扩增出等位基因1~16个不等, 共计356个等位基因。结果表明: (1)5个群体检测的有效等位基因数在1.07~12.30个不等, 平均多态信息含量为0.74、0.74、0.69、0.75和0.75, 无偏期望杂合度的平均值为0.74、0.78、0.70、0.76和0.78, 说明这几个群体属于高度多态, 遗传多样性水平较高。(2)群体间相似系数在0.52以上, 相似性较高。聚类分析显示, 东岗、奉城和辽中3个养殖场的德国镜鲤群体聚类成一个分支, 而德国镜鲤选育系与松浦群体聚类成另一分支。聚类的先后与它们在地理分布上距离远近有一定的相关性。(3)在与功能基因相关的多个微卫星基因座位上, 扩增产物呈现不同程度的缺失现象, 这些无效等位基因的产生可能与结构基因在育种中受到人工选择的影响较大有关。     

Assessment of population genetic structure in common wild rice Oryza rufipogon Griff. using microsatellite and allozyme markers

The genetic structure of five natural populations of common wild rice Oryza rufipogon Griff. from China, was investigated with 21 microsatellite loci and compared to estimates of genetic diversity and genetic differentiation detected by 22 allozyme loci. Microsatellite loci, as expected, have much higher levels of genetic diversity (mean values of A = 3.1, P = 73.3%, Ho = 0.358 and He = 0.345) than allozyme loci (mean values of A = 1.2, P = 12.7%, Ho = 0.020 and He = 0.030). Genetic differentiation detected by microsatellite loci ( FST = 0.468, mean I = 0.472) was higher than that for allozyme loci ( FST =0.388, mean I = 0.976). However, microsatellite markers showed less deviation from Hardy-Weinberg expectation (Wright's inbreeding coefficient FIS = -0.069) than do allozymes ( FIS = 0.337). These results suggest that microsatellite markers are powerful high-resolution tools for the accurate assessment of important parameters in population biology and conservation genetics of O. rufipogon, and offer advantages over allozyme markers.     

卧龙圈养大熊猫遗传多样性现状及预测

以中国最大的大熊猫圈养种群—四川卧龙中国大熊猫保护中心的圈养种群为对象,以８个大熊猫微卫星位点为分子标记, 探讨了大熊猫圈养种群的遗传多样性, 并与邛崃野生种群及其他７个濒危物种进行比较。微卫星数据表明, 圈养种群的遗传多样性水平(A＝5.5, He ＝0.620, Ho＝0.574) 低于邛崃野生种群(A＝9.8,He＝0.779,Ho＝0.581),但高于其他7 个濒危物种的种群(He＝0.13~0.46)。在此数据的基础上对未来100个世代内圈养种群遗传多样性的变化情况做出了预测。结果表明假设种群数量比现在扩大一倍, 经历100个世代后也只会使平均等位基因数少减少0.4。因此继续增加野生个体对保持遗传多样性的意义已经不大, 建议该圈养种群的保护策略应将重点放到制定更有效的繁殖计划以避免近交上。     

Genetic diversity of a rare species Aristolochia contorta bungae (aristolochiaceae) in Primorsky Krai

The herbaceous vine, twisted birthwort Aristolochia contorta Bunge, is a rare species listed in the Red Data Book of Primorsky krai (2008). On the northern boundary of its range (south of the Russian Far East), the species is represented by small isolated populations confined to the river drainages. Using allozyme analysis, genetic variation of nine natural populations ofA. contorta (247 accessions), which represented the main part of the species range in Russia, was examined. The values of genetic variation indices (P = 22.7%; A = 1.28; Ho = 0.129; He = 0.101) were low and comparable with the data obtained for other rare plants. The proportion of unique genotypes (G/N) and Simpson's genotypic diversity index (D) ranged from 0.32 to 0.64 and from 0.60 to 0.98, respectively. This means that A. contorta is characterized by sexual and asexual reproduction. Moreover, the ratio between these types of reproduction varied among the populations. Complete absence of inbreeding and excess of heterozygotes (F(IS) = -0.282), which was low probable in case of free mating, was observed. Evidently, clonal growth and (or) apomixis enables the species to maintain certain level of heterozygosity despite of small population sizes and non-regular gene exchange.     

Allozyme polymorphism and phylogenetic relationships in Apis mellifera subspecies selectively reared in Poland and Bulgaria

The genetic variability of honey bee populations of three subspecies selectively reared in Poland (A. m. carnica and A. m. caucasica) and Bulgaria (A. m. macedonica-type rodopica) was studied using isoenzyme analysis of six enzyme systems (MDH-1, ME, EST-3, ALP, PGM and HK) corresponding to 6 loci. All loci were found to be polymorphic in the studied populations. Three alleles were detected at each locus: MHD-1 (MDH65, MDH80 and MDH100), Me (ME90, ME100 and ME106), EST-3 (EST94, EST100 and EST118), ALP (ALP80 ALP90 and ALP100), PGM (PGM80, PGM100 and PGM114) and HK (HK87, HK100 and HK110). The observed and expected heterozygosities (Ho and He) ranged from 0.196 (A. m. macedonica SM) to 0.265 (A. m. carnica MV) and from 0.224 (A. m. macedonica SM) to 0.273 (A. m. carnica GR), respectively. Allele frequencies of all loci were used to estimate Nei's (1972) genetic distance, which was found to range from 0.003 (between A. m. macedonica TR and SM and between A. m. carnica GR and MV populations) to 0.057 (between A. m. macedonica SM and A. m. caucasica populations). The estimated mean F(ST) value from allozyme data was 0.0364. A UPGMA dendrogram was obtained by genetic distance matrix methods; A. m. macedonica (type rodopica), A. m. carnica and A. m. caucasica populations represented different clades.     

Improved dairy cattle mating plans at herd level using genomic information

From 2012 to 2018, 223 180 Montbéliarde females were genotyped in France and the number of newly genotyped females increased at a rate of about 33% each year. With female genotyping information, farmers have access to the genomic estimated breeding values of the females in their herd and to their carrier status for genetic defects or major genes segregating in the breed. This information, combined with genomic coancestry, can be used when planning matings in order to maximize the expected on-farm profit of future female offspring. We compared different mating allocation approaches for their capacity to maximize the expected genetic gain while limiting expected progeny inbreeding and the probability to conceive an offspring homozygous for a lethal recessive allele. Three mate allocation strategies (random mating (RAND), sequential mating (gSEQ€) and linear programing mating (gLP€)) were compared on 160 actual Montbéliarde herds using male and female genomic information. Then, we assessed the benefit of using female genomic information by comparing matings planned using only female pedigree information with the equivalent strategy using genomic information. We measured the benefit of adding genomic expected inbreeding and risk of conception of an offspring homozygous for a lethal recessive allele to Net merit in mating plans. The influence of three constraints was tested: by relaxing the constraint on availability of a particular semen type (sexed or conventional) for bulls, by adding an upper limit of 8.5% coancestry between mate pairs or by using a more stringent maximum use of a bull in a herd (5% vs 10%). The use of genomic information instead of pedigree information improved the mate allocation method in terms of progeny expected genetic merit, genetic diversity and risk to conceive an offspring homozygous for a lethal recessive allele. Optimizing mate allocation using linear programming and constraining coancestry to a maximum of 8.5% per mate pair reduced the average coancestry with a small impact on expected Net Merit. In summary, for male and female selection pathways, using genomic information is more efficient than using pedigree information to maximize genetic gain while constraining the expected inbreeding of the progeny and the risk to conceive an offspring homozygous for a lethal recessive allele. This study also underlines the key role of semen type (sexed vs conventional) and the associated constraints on the mate allocation algorithm to maximize genetic gain while maintaining genetic diversity and limiting the risk to conceive an offspring homozygous for a lethal recessive allele.