An independent confirmation of a quantitative trait locus for milk yield and composition traits on bovine chromosome 26

Several reports have demonstrated that bovine chromosome 26 (BTA26) harbours significant or suggestive quantitative trait loci (QTL) for milk production and composition traits in dairy cattle. Our previous study showed that a C/T substitution in the bovine TCF7L2 gene on BTA26 was significantly linked to QTL for protein yield (PY) in a Canadian dairy cattle population. Actually, this polymorphism was one of the markers derived from a genome‐wide screening of QTL for milk PY using an amplified fragment length polymorphism technique combined with a DNA pooling strategy. In the present study, 990 Holstein bulls with complete genotype and phenotype data from 14 sire families were analysed to confirm, if the QTL effects exist in other populations. Statistical analysis revealed that this marker was significantly associated with PY, protein percentage, milk yield and fat yield (FY) (p < 0.001) in the US Holstein population. These results indicate that this QTL region has a pleiotrophic effect on different milk traits and is portable in different populations.     

Genetic parameters for total lactation yields of milk,fat, protein,and somatic cell score in New Zealand dairy goats

The aim of this study was to estimate genetic parameters for lactation yields of milk (MY), fat (FY), protein (PY), and somatic cell score (SCS) of New Zealand dairy goats. The analysis used 64,604 lactation records from 23,583 does, kidding between 2004 and 2017, distributed in 21 flocks and representing 915 bucks. Estimates of genetic and residual (co) variances, heritabilities, and repeatabilities were obtained using a multiple‐trait repeatability animal model. The model included the fixed effects of contemporary group (does kidding in the same flock and year), age of the doe (in years), and as covariates, kidding day, proportion of Alpine, Nubian, Toggenburg, and “unknown” breeds (Saanen was used as the base breed), and heterosis. Random effects included additive animal genetic and doe permanent environmental effects. Estimates of heritabilities were 0.25 for MY, 0.24 for FY, 0.24 for PY, and 0.21 for SCS. The phenotypic correlations between MY, FY, and PY ranged from 0.90 to 0.96, and the genetic correlations ranged from 0.81 to 0.93. These results indicate lactation yield traits exhibit useful heritable variation and that multiple trait selection for these traits could improve milk revenue produced from successive generations of New Zealand dairy goats.     

Random regression test day models to estimate genetic parameters for milk yield and milk components in Philippine dairy buffaloes

Heritabilities and genetic correlations for milk production traits were estimated from first‐parity test day records on 1022 Philippine dairy buffalo cows. Traits analysed included milk (MY), fat (FY) and protein (PY) yields, and fat (Fat%) and protein (Prot%) concentrations. Varying orders of Legendre polynomials (Leg_m) as well as the Wilmink function (Wil) were used in random regression models. These various models were compared based on log likelihood, Akaike's information criterion, Bayesian information criterion and genetic variance estimates. Six residual variance classes were sufficient for MY, FY, PY and Fat%, while seven residual classes for Prot%. Multivariate analysis gave higher estimates of genetic variance and heritability compared with univariate analysis for all traits. Heritability estimates ranged from 0.25 to 0.44, 0.13 to 0.31 and 0.21 to 0.36 for MY, FY and PY, respectively. Wilmink's function was the better fitting function for additive genetic effects for all traits. It was also the preferred function for permanent environment effects for Fat% and Prot%, but for MY, FY and PY, the Leg_m was the appropriate function. Genetic correlations of MY with FY and PY were high and they were moderately negative with Fat% and Prot%. To prevent deterioration in Fat% and Prot% and improve milk quality, more weight should be applied to milk component traits.     

Growth, slaughter performance and feeding behaviour of young bulls belonging to three native cattle breeds raised in the Alps

Most studies on lactation curves only consider milk yield and describe a standard lactation curve of dairy cows, showing a peak or maximum daily yield occurring between 4 and 8 weeks after calving, followed by a daily decrease in milk yield until the cow is dried off. Wood's model is a widely used lactation curve function. Wood's model was fitted to test-day records of 95,405 lactations of parities lower than 5. Milk traits were milk yield (MY), fat percentage (F%), protein percentage (P%), fat yield (FY) and protein yield (PY), and the lactation curve was individually considered as a cluster of five linked curves. Milk trait and parity influence the goodness of fit of Wood's model. In 19.3% of the lactations, the shape of the MY, FY and PY curves follows the standard lactation curve while F% and P% have the reversed standard shape. The initial phase of lactation with the FY and PY curves contributes to the high variability of shapes.     

Genetic analysis of liability to clinical mastitis, with somatic cell score and production traits using bivariate threshold–linear and linear–linear models

Inferences about genetic and residual correlation estimates and sire evaluations involving a categorical trait with linear model are ambiguous and mostly based on data simulations. In this study, estimates of variance components and prediction of breeding values in a model with a categorical and a continuous trait were compared between threshold–linear (TLM) and linear–linear models (LLM) in analysis of large clinical mastitis (CM) field data. Data on CM, somatic cell score (SCS), 305-day milk (MY), protein (PY) and fat yield (FY) from first-lactation Finnish Ayrshire cows were used. Four bivariate analyses were made using a TLM in Bayesian analysis. Each analysis fitted CM and one continuous trait at a time. Corresponding bivariate analyses were made using a Gaussian linear model. Estimates of heritabilities for CM were 0.06 and 0.02 from TLM and LLM, respectively whilst heritability estimates of the continuous traits were similar from both models. Genetic correlations between CM–SCS, CM–MY, CM–PY, and CM–FY from TLM and LLM were 0.63 and 0.63; 0.36 and 0.36; 0.32 and 0.32; 0.30 and 0.29, respectively. Estimates of residual correlations were 0.11 and 0.06; − 0.04 and − 0.02; − 0.03 and − 0.02; − 0.05 and − 0.03 between CM–SCS, CM–MY, CM–PY, and CM–FY, respectively. Comparison between the models indicates similar estimates of genetic correlations with no underestimation with the linear model analysis. In CM evaluation, the comparison of model's predictive ability showed greater improvements in accuracy with the bivariate than with the univariate models. There was, however no clear advantage of univariate threshold model over univariate linear model, except for less accuracy sires.     

Mapping of quantitative trait loci for lactation persistency traits in German Holstein dairy cattle

A whole genome scan to map quantitative trait loci (QTL) for persistency of milk yield (PMY), persistency of fat yield (PFY), persistency of protein yield (PPY) and persistency of milk energy yield (PEY) was performed in a granddaughter design in the German Holstein dairy cattle population. The analysis included 16 paternal half‐sib families with a total of 872 bulls. The analysis was carried out for the first lactation and for the first three lactations combined using univariate weighted multimarker regression. Controlling the false discovery rate across traits and data sets at a level of 0.15 and treating the four persistency traits as different traits revealed 27 significant QTL. A total of 12 chromosomes showed significant QTL effects on a chromosomewise basis. The DGAT1 effect was highly significant for PPY and protein yield. A haplotype analysis using results of previous studies of the same design revealed a co‐segregation of various persistency QTL and QTL affecting health traits like dystocia and stillbirth and functional traits like non‐return rate 90 and somatic cell score.     

Multiple QTL on chromosome six in dairy cattle affecting yield and content traits

A granddaughter design containing five half-sib families from German Holstein–Friesian cattle was subjected to QTL analysis starting from the hypothesis of the existence of more than one QTL on chromosome BTA 6 affecting milk yield, fat yield, protein yield and content of fat and protein. The marker map consisted of 16 microsatellite markers with marker heterozygosity varying from 0.44 to 0.94. Two statistical methods were used: least squares (LS) and residual maximum likelihood (REML) allowing for two QTL simultaneously. The test statistics were calculated in steps of one cM along the chromosome. Significant QTL at the chromosome-wise 5% level according to the permutation test critical value were detected mainly in single families. The results were in conformance with the findings of several previous studies with approximate positions of putative QTL at 49 cM for milk yield, at 70 cM for fat and protein yield, and at 46 cM for protein content. Further QTL positions were suggested mostly for yield traits and protein content in the area of the casein gene cluster at 90…95 cM. The results of the two-QTL model analyses when using LS led to family specific inferences of a second QTL for fat yield and content of protein and fat, partly supported by the epistasis model.     

Estimation of genetic parameters and genome scan for 15 semen characteristics traits of Holstein bulls

A QTL detection experiment was performed in French dairy cattle to search for QTL related to male fertility. Ten families, involving a total of 515 bulls, were phenotyped for ejaculated volume and sperm concentration, number of spermatozoa, motility, velocity, percentage of motile spermatozoa after thawing and abnormal spermatozoa. A set of 148 microsatellite markers were used to realize a genome scan. First, genetic parameters were estimated for all traits. Semen production traits were found to have moderate heritabilities (from 0.15 to 0.30) while some of the semen quality traits such as motility had high heritabilities (close to 0.60). Genetic correlations among traits showed negative relationships between volume and concentration and between volume and most quality traits such as motility or abnormal sperm while correlations between concentration and these traits were rather favourable. Percentages of abnormal sperm were negatively related to quality traits, especially with motility and velocity of spermatozoa. Three QTL related to abnormal sperm frequencies were significant at p < 0.01. In total, 11 QTL (p < 0.05) were detected. However, the number of QTL detected was within the range of expected false positives. Because of the lack of power to find QTL in this design further analyses are required to confirm these QTL.     

Effects of Acyl-CoA:diacylglycerol acyl transferase 1 (DGAT1) gene on milk production traits in crossbred Holstein dairy cattle

The objective of this study was to analyze and investigate the genotype frequency and the association between Acyl-CoA:diacylglycerol acyltransferase1 gene, DGAT1 gene, and milk yield (MY), milk composition, protein yield (PY), fat yield (FY), solid not fat yield (SNF), total solid (TS), the content of fat, protein, solid not fat, and total solid, (%Fat,%Prot,%SNF,%TS) in two herds of crossbred Holstein dairy cattle in Thailand. Two hundred and twenty-seven crossbred Holstein cows were used and their blood samples were taken for the study. PCR–RFLP was used to identify the allele and genotype of DGAT1 gene. A general linear model and the least square method were used to estimate the least square mean and additive, and the dominant effect of the gene on the traits and the least significant differences were used to compare the mean of each trait between genotypes. Two alleles (K, A) and three genotypes (AA, KA, KK) were detected, the highest allele and genotype frequencies were A and AA, respectively. The least mean squares of each genotype were compared and significant differences between genotype were detected. Genotype KK has the greatest effect on all milk composition content traits, while genotype AA has the greatest effect on yield traits. Highly significant additive gene effect was detected. From the results, it can be concluded that the DGAT1 gene can be used as a gene marker for assisted selection in milk composition traits.     

Quantitative trait loci for milk production and functional traits in two Danish Cattle breeds

Quantitative trait loci (QTL) in Danish Jersey and Danish Red cattle were independently mapped by least squares regression analysis. For Jersey breed, five grandsire families were genotyped for 186 markers on 16 chromosomes (BTAs). Eight traits analysed were milk yield (MY), fat percentage (FP), protein percentage (PP), clinical mastitis (CM), somatic cell score (SCS), maternal stillbirth, maternal calf size (MCS) and maternal calving difficulty. For Red breed, nine grandsire families were genotyped for 166 markers on 18 BTAs. Six traits analysed were MY, FP, PP, CM, SCS and female fertility. Nine and five QTL were detected in Jersey and Red breed, respectively, in across family tests. In Jersey breed, the results indicate QTL for CM and MCS on BTA 3. Additionally, there is an indication of QTL for MCS and FP on BTA 1 and a tentative evidence for a QTL for MY on BTA 26. There is a high risk of detected QTL being false positives. The detected QTL in Jersey breed indicate interesting results from a breeding perspective, but a practical application should await genome-wide association studies.     

中国荷斯坦牛PIN1基因对产奶性状的遗传效应分析

前期研究通过荷斯坦公牛全基因组重测序鉴定到17个奶牛产奶性状候选功能基因,其中,肽基脯氨酸顺反异构酶基因(PIN1)参与甘油三酯代谢、甘油磷脂代谢以及mTOR信号通路,且位于产奶量和乳蛋白量性状QTL区间。为进一步系统分析PIN1基因是否对奶牛产奶性状具有遗传效应,本实验基于40头公牛的基因组DNA混池,采用PCR产物直接测序法对PIN1基因的全部编码区以及上下游调控区2000 bp进行扫描,在内含子2检测到1个SNP位点7:g.14432394G>A,A、G等位基因频率分别为0.4797和0.5203。采用靶向测序基因型技术对北京地区987头中国荷斯坦母牛进行个体基因型检测,对SNP位点7:g.14432394G>A与5个产奶性状进行关联分析。结果表明:在第1泌乳期,SNP 7:g.14432394G>A与产奶量、乳脂量、乳蛋白量和乳蛋白率呈显著或极显著关联(P=0.0001~0.0493);在第2泌乳期,SNP与产奶量、乳脂量、乳脂率和乳蛋白量呈显著或极显著关联(P=0.0001~0.0104);SNP位点7:g.14432394G>A对产奶量、乳脂量、乳蛋白量和乳蛋白率的加性效应或等位基因替代效应均达到显著或极显著。综上,PIN1基因对中国荷斯坦牛的产奶量和乳蛋白、乳脂性状具有显著遗传效应,可作为遗传标记用于基因组选择,以加快遗传进展。     

Identification of candidate markers on bovine chromosome 14 (BTA14) under milk production trait quantitative trait loci in Holstein

The objective of this study was to identify single-nucleotide polymorphisms using a bovine chromosome 14 high-density SNP panel after accounting for the effect of DGAT1. Linkage disequilibrium information and sire heterozygosity were used to select markers for linkage analysis on bovine chromosome 14 for milk production traits in 321 Holstein animals. Results show putative milk peaks at 42 and 61 cM, both at p<0.10, a fat yield peak at 42 and 63 cM, both at p<0.05; a protein yield peak at 42 (p<0.01) and 84 cM (p<0.05); fat per cent peaks at 3 (p<0.01) and 29 cM (p<0.05), and a protein per cent peak at 4 cM (p<0.05). Once quantitative trait loci positions were established, allele substitution effects for all markers were evaluated using the same statistical model. Overlaying information between quantitative trait loci (QTL) and allele effect analysis enabled the identification (p<0.01) of 20 SNPs under the milk yield QTL, 2 under both of the fat yield peaks, 8 and 9 under the protein yield peaks, 2 and 6 for the fat per cent peaks and 5 for the protein per cent peak. One SNP in particular, ss61514555:A>C, showed association with 3 of the 5 traits: milk (p=1.59E-04), fat (p=6.88E-05) and protein yields (p=5.76E-05). Overall, combining information from linkage disequilibrium, sire heterozygosity and genetic knowledge of traits enabled the characterization of additional markers with significant associations with milk production traits.     

Short communication: investigation of the feasibility of genomic selection in Icelandic Cattle

Icelandic Cattle is a local dairy cattle breed in Iceland. With about 26,000 breeding females, it is by far the largest among the indigenous Nordic cattle breeds. The objective of this study was to investigate the feasibility of genomic selection in Icelandic Cattle. Pedigree-based best linear unbiased prediction (PBLUP) and single-step genomic best linear unbiased prediction (ssGBLUP) were compared. Accuracy, bias, and dispersion of estimated breeding values (EBV) for milk yield (MY), fat yield (FY), protein yield (PY), and somatic cell score (SCS) were estimated in a cross validation-based design. Accuracy (r^) was estimated by the correlation between EBV and corrected phenotype in a validation set. The accuracy (r^) of predictions using ssGBLUP increased by 13, 23, 19, and 20 percentage points for MY, FY, PY, and SCS for genotyped animals, compared with PBLUP. The accuracy of nongenotyped animals was not improved for MY and PY, but increased by 0.9 and 3.5 percentage points for FY and SCS. We used the linear regression (LR) method to quantify relative improvements in accuracy, bias (Δ^), and dispersion (b^) of EBV. Using the LR method, the relative improvements in accuracy of validation from PBLUP to ssGBLUP were 43%, 60%, 50%, and 48% for genotyped animals for MY, FY, PY, and SCS. Single-step GBLUP EBV were less underestimated (Δ^), and less overdispersed (b^) than PBLUP EBV for FY and PY. Pedigree-based BLUP EBV were close to unbiased for MY and SCS. Single-step GBLUP underestimated MY EBV but overestimated SCS EBV. Based on the average accuracy of 0.45 for ssGBLUP EBV obtained in this study, selection intensities according to the breeding scheme of Icelandic Cattle, and assuming a generation interval of 2.0 yr for sires of bulls, sires of dams and dams of bulls, genetic gain in Icelandic Cattle could be increased by about 50% relative to the current breeding scheme.     

中国荷斯坦牛RPL23A和ACACB基因对产奶性状的遗传效应分析

作者所在团队前期通过奶牛乳腺上皮组织转录组测序及荷斯坦公牛全基因组重测序研究发现RPL23A和ACACB基因是奶牛乳蛋白和乳脂性状的候选功能基因,本研究旨在探究这两个基因是否对奶牛产奶性状具有显著遗传效应。以北京地区7个牧场的1059头中国荷斯坦母牛为试验群体,采集尾根静脉血并提取基因组DNA,通过飞行时间质谱方法检测SNP位点基因型,利用SAS9.4软件的MIXED过程进行关联分析。结果表明,RPL23A基因的SNP位点g.20146771C>T与第1泌乳期5个产奶性状达到显著或极显著关联(P=0.0001~0.0416),其优势等位基因为T;ACACB基因的g.63878254T>C位点与第1泌乳期产奶量、乳脂量和乳蛋白量呈极显著关联(P<0.01),其优势等位基因为C;g.63962768G>A位点与第1泌乳期产奶量、乳脂量、乳脂率和乳蛋白率关联显著或极显著(P=0.0001~0.0391),其优势等位基因为A。综上,RPL23A基因主要影响中国荷斯坦牛产奶量和乳蛋白,ACACB基因对产奶量和乳脂具有显著遗传效应,3个SNP位点可考虑作为遗传标记用于标记辅助选择培育奶牛高乳蛋白乳脂新品系和选育提高。     

Evaluation of association between polymorphism within the thyroglobulin gene and milk production traits in dairy cattle

In dairy cattle, many studies have reported quantitative trait loci (QTL) on the centromeric end of chromosome 14 that affect milk production traits. One of the candidate genes in this QTL region – thyroglobulin (TG) – was previously found to be significantly associated with marbling in beef cattle. Thus, based on QTL studies in dairy cattle and because of possible effects of this gene on fat metabolism, we investigated the association of TG with milk yield and composition in Holstein dairy cattle. A total of 1279 bulls from the Cooperative Dairy DNA Repository Holstein population were genotyped for a single nucleotide polymorphism in TG used previously in beef cattle studies. Analysis of 29 sire families showed no significant association between TG variants and milk production traits. Within‐sire family analysis suggests that TG is neither the responsible gene nor a genetic marker in association with milk production traits.     

Searching for DNA markers for milk production and composition on chromosome 6 in sheep

Several milk protein polymorphisms are potential tools for selection in dairy ruminants. However, research results for dairy sheep are not as conclusive as those for goats or cattle and are often controversial. The main objective of this study was to find and later use molecular genetic markers in selection to improve milk production and milk composition in Awassi ewes. Chromosome 6 was chosen because several studies have reported the presence of significant quantitative trait loci (QTL) affecting milk production traits on ovine and bovine chromosome 6. Altogether, genotypes for 13 microsatellite loci were determined for 258 ewes, which were purebred Awassi or Awassi-Merino crosses. Phenotypic data were lactation yield of milk, milk fat, protein and lactose (kg), average milk protein and fat percentage and average somatic cell count. Five out of the 13 microsatellites showed significant association with at least one of the examined traits.     

Fine mapping of a calving QTL on Bos taurus autosome 18 in Holstein cattle

Decreased calving performance not only directly impacts the economic efficiency of dairy cattle farming but also influences public concern for animal welfare. Previous studies have revealed a QTL on Bos taurus autosome (BTA) 18 that has a large effect on calving traits in Holstein cattle. In this study, fine mapping of this QTL was performed using imputed high‐density SNP chip (HD) genotypes followed by imputed next‐generation sequencing (NGS) variants. BTA18 was scanned for seven direct calving traits in 6113 bulls with imputed HD genotypes. SNP rs136283363 (BTA18: 57 548 213) was consistently the most significantly associated SNP across all seven traits [e.g. p‐value = 2.04 × 10^?59 for birth index (BI)]. To finely map the QTL region and to explore pleiotropic effects, we studied NGS variants within the targeted region (BTA18: 57 321 450–57 625 355) for associations with direct calving traits and with three conformation traits. Significant variants were prioritized, and their biological relevance to the traits was interpreted. Considering their functional relationships with direct calving traits, SIGLEC12, CD33 and CEACAM18 were proposed as candidate genes. In addition, pleiotropic effects of this QTL region on direct calving traits and conformation traits were observed. However, the extent of linkage disequilibrium combined with the lack of complete annotation and potential errors in the Bos taurus genome assembly hampered our efforts to pinpoint the causal mutation.     

Mapping genes for fatness and growth on pig chromosome 13: a search in the region close to the pig PIT1 gene

Previous research has shown that PIT1 polymorphisms in several resource populations and the chromosomal region near PIT1 in some populations have been significantly associated with fatness and growth QTLs on pig chromosome 13. To confirm these previous results and to clarify the role of the PIT1 gene in the putative QTL region, this research project was enlarged to include two microsatellite markers flanking each side of the PIT1 gene ( Swr1008 , S0068 , Sw398 and Sw1056 ). The ISU Chinese × US resource families were used and the traits analysed were birth weight, 21 day weight, 42 day weight, longissimus muscle area, back-fat thickness at several locations, meat colour, marbling and firmness on the carcass, and growth rate for selected time periods. The total number of F₂ pigs used ranged from 241 to 330. The data were analysed using interval mapping for each breed-cross separately as well as with the pooled data, and single marker least squares analyses for the pooled data. Significant evidence of a QTL for first rib back-fat thickness was detected approximately 20 cM from the PIT1 gene by using both single marker (p < 0.01) and interval mapping analyses in the pooled data (p < 0.0001) as well as in one family (p < 0.01). Evidence of a QTL for birth weight was detected at the estimated PIT1 position in the interval mapping analysis by using the pooled data (p < 0.014) and verified by the single marker analyses. These results confirmed the previously published QTL work on pig chromosome 13 for the birth weight QTL but suggest that other genes in the region may be partly responsible for the earlier results on the back-fat thickness QTL in our resource families.     

公牛家系泌乳曲线的研究

本文根据北京黑白花奶牛２２个公牛家系的女儿泌期资料，利用Ｗｏｏｄ模型估计了各公牛家系的泌乳曲线参数，并且按照家系内女儿的不同胎次，所在牧场和产犊年份分组作了更加深入的研究。所考虑的曲线参数为规模因子ａ。产奶量上升率ｂ和下降率ｃ；次级参数包括３０５天实际产奶量，３０５天估计产奶量，高峰月份，高峰月产奶量和泌乳持久力。结果表明，与低产公牛家系相比，高产公牛家系的泌乳曲线通常具有较高的初始产奶量，参数ａ     

Assessment of positional candidate genes myf5 and igf1 for growth on bovine chromosome 5 in commercial lines of Bos taurus

Quantitative trait loci for growth traits in beef cattle have been previously reported and fine-mapped in three chromosomal regions of 0 to 30 cM, 55 to 70 cM, and 70 to 80 cM of bovine chromosome 5. In this study, we further examined the association between gene-specific single nucleotide polymorphisms (SNP) of two positional candidate genes, bovine myogenic factor 5 (myf5) and insulin-like growth factor-1 (igf1), in the QTL regions and the birth weight (BWT), preweaning average daily gain (PWADG), and average daily gain on feed (ADGF) in commercial lines of Bos taurus. The QTL regions for the growth traits identified using a haplotype association analysis, which included the gene-specific SNP markers for both genes in this study, were in agreement with previous studies. The gene-specific SNP marker association analysis indicated that the SNP in myf5 had a significant additive effect on PWADG in the M1 line of Beefbooster Inc. (P < 0.10), and a significant additive effect (P < 0.05) and a significant dominance effect (P < 0.10) on ADGF in the M3 line of Beefbooster Inc. When the data from the two commercial lines were pooled, the SNP in myf5 showed a significant association with PWADG (P < 0.10) and with ADGF (P < 0.05). The association between the SNP and BWT, however, did not reach a significance level in the M1 line, the M3 line, or across the lines. For igf1, no significant association between the SNP and the growth traits was detected in either the M1 line or the M3 line, whereas there was only a significant dominance effect (P < 0.10) on BWT detected for the SNP in igfl when the data from the two commercial lines were pooled. These results suggest that myf5 is a strong candidate gene that influences PWADG and ADGF in beef cattle. The SNP of igf1 may not be a causative or close to the causative mutation that affects the three growth traits in the populations of beef cattle examined in this study. Other SNP of igf1 and myf5 or other genes in their respective chromosomal regions, however, should also be studied.