Litter size is an important economic trait in the goat industry. Previous
studies on the bone morphogenetic protein 15 (
Goats are spread all around the world, especially in harsh and marginal regions. They play an important economic role in developing countries (Araújo et al., 2010). The goat population is increasing in developing countries due to their different food consumption patterns and lower water requirements in comparison with other livestock species such as cattle and sheep (Moghadaszadeh et al., 2015). Goats are raised for meat, milk and hair, particularly mohair or cashmere production, and it is clear that highly productive goats can improve the quality and increase the quantity of the mentioned products (Jalbani et al., 2017).
In recent years, the improvement of reproductive traits, such as litter size
(LS), has become one of the great interests of breeders and local farmers, and
consequently, research efforts have been made to unravel these traits' genetic
basis (Eghbalsaied et al., 2009). Although litter size is a complex trait
influenced by numerous genes and environmental factors, some major genes
have been identified to influence litter size (Lai et al., 2016). Among
them is the bone morphogenetic protein 15 (
For the variant c.963A
These studies on fertility traits in livestock, especially on the
Meta-analysis is a quantitative and formal study design used to assess the
previous findings of researchers about specific questions to obtain a more
validated conclusion about that type of research. Outcomes from a
meta-analysis can provide a more precise estimate of the effect of
treatments or other factors on a trait than any single study because of
pooled results included in the analysis (Lean et al., 2009). Some
meta-analyses have been conducted on litter size in goats (Mahmoudi et al.,
2019) and milk-related traits in cattle (Mahmoudi et al., 2020) and small
ruminants (Razmkabir et al., 2021). To the best of our knowledge, no
meta-analysis has been conducted on association of detected SNPs in the
The preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist criteria were used to identify eligible studies for this meta-analysis. Two investigators (Emel Zergani and Jalal Rostamzadeh) independently searched databases including Springer, ScienceDirect, Wiley and PubMed to detect studies relevant to our question using combination of search terms as follows: “BMP15”, “SNP”, “polymorphism”, “prolificacy”, “litter size”, “capra hircus” and “goat”. Furthermore, we explored all Chinese and Persian journals and databases to find articles published in different languages. In addition, we scrutinized reference lists of extracted articles to assure that no articles were missed. All articles which were in the form of an abstract or review and also any kind of duplication were removed, and the quality of remaining full-text articles was appraised by two investigators. Finally, the third investigator (Amir Rashidi) resolved all conflicts and disagreements for inclusion and exclusion of studies.
Characteristics of studies included in this meta-analysis.
NE: not existent.
The heterogeneity test results for genetic models.
The outcomes of meta-analysis of the association between the c.963A
SMD: standardized mean difference.
Forest plot of association between c.963A
Studies were eligible if they met the following criteria: (1) report on
c.963A
The data included in our meta-analysis were extracted from selected studies based on designated inclusion and exclusion criteria. The extracted data included the first name of the author, year of publication, goat breed and sample size, LSM, and standard error reported for each genotype.
Considering that the standard deviations are needed to analyze data, we
employed the following equation to calculate SD from sample sizes of genotypes
and standard errors of the LSM:
ReviewManager v5.0 software was used to analyze data collected from
different studies employing recessive (
In the next stage, Cochran's
This method of studies contains the primary components of a systematic review and meta-analysis. The identification stage is the first stage, and second is the development of a detailed protocol and its preregistration. Searching two literature databases at least, along with other sources of published studies (using reviews, field experts, own data, non-English literature), is recommended. It is necessary to mention search dates and exact keyword threads.
The screening and eligibility stage should be based on the inclusion and exclusion criteria studies. Criteria might differ for the initial screening (title, abstract) compared to the full-text screening, but both need to be reported in detail. At least two investigators should study and decide on the selection of eligible articles, with a plan for disagreement resolution and calculating disagreement rates. The list of studies excluded at the full-text screening stage, with reasons for their exclusion, and a full list of studies included in the final dataset, with their basic characteristics, are reported. We recorded the figures and tables as well as reported intermediate calculations, transformations, simplifications and assumptions made during data extraction. These details make identifying mistakes easier and modify reproducibility. Documentation included a summary of the dataset, information on data and study details that authors reported, a short explanation of software used for analyses. Therefore, we created a PRISMA diagram (Fig. 1), which records the starting information from the studies and leads to the final dataset (Nakagawa et al., 2017).
The PRISMA flowchart showing inclusion and exclusion criteria.
A total of 38 articles were identified through search on databases including PubMed, ScienceDirect, Wiley Online Library, CNKI (Chinese) and Magiran (Iranian).
In addition to the abstracts, a total of five duplicate studies were removed. Then, we screened the remaining publications to exclude irrelevant studies, resulting in deletion of nine articles which did not investigate the SNP and/or trait of interest. Furthermore, in some studies polymorphisms have been reported, but their association with litter size was not evaluated; thus these studies were also rejected. In conclusion, five studies involving 978 goats were selected to be included in our meta-analysis, three of which were written in English, one in Persian and the last one in Chinese. Among the selected studies, two pieces of research were conducted on different breeds of goats; thus each breed was evaluated as a separate study in the meta-analysis. Characteristics of included studies are presented in Table 1.
Table 2 involves Cochran's
The results of meta-analysis of association between the SNP and trait of
interest under four genetic models are summarized in Tables 3–7. The
estimates did not show any association between the c.963A
The sensitivity analysis was performed to investigate the robustness and
validity of the meta-analysis using a leave-one-out approach. We did not
observe any difference in pooled results of SMDs before and after removing
one study in dominant, recessive, additive and co-dominant genetic models.
The funnel plots for studies drawn in all genetic models are depicted in
Fig. 2. As is observable, the shape of all plots indicates no
publication bias under all four employed models. On the contrary,
sensitivity analysis showed significant difference in litter size by
dropping studies performed by Dong and Du (2010) on the Lubei White breed and by
Feng et al. (2014) and Moghadaszadeh et al. (2015) under the additive model
(Table 8 and Fig. 3). Furthermore, the results of Egger's regression test
obtained for all four comparison models showed no evidence of publication
bias at the level of
Funnel plots for the publication bias under the dominant model
Funnel plots of sensitivity analysis under the additive model, with the
Dong and Du (2010) Lubei White breed study removed
It is important to understand the genetic regulation of reproduction traits
in livestock (Nicol et al., 2009). The
Association of the litter size with some important genes, especially
Forest plot of association between c.963A
In research on genetic mutations and effects on the ovulation rate in sheep,
results have shown that
Niu et al. (2021) worked on the importance of
Results of a study on Luzhong mutton sheep stated the association between
litter size and
Jiao et al. (2007) and Chu et al. (2007) reported that novel SNPs (A963G)
and (C1050G), which were identified in exon 2 of
Interestingly, the mutation of the A963G of the
Forest plot for association between c.963A
Forest plot of association between c.963A
Forest plots of sensitivity analysis under the additive model, with the
Dong and Du (2010) Lubei White breed study removed
To the best of our knowledge, no meta-analysis has been conducted on
the association of the A963G variant with litter size in goats. The meta-analyses
of data under recessive and co-dominant models did not show evidence of
association between the SNP and litter size (Tables 5 and 7). However, we
observed significant association of A963G polymorphism with litter size
under the dominant and additive models (Tables 4 and 6). In Table 4, the
diamond lies entirely to the left side of the line of no effect, suggesting a
significant difference in litter size between animals with
Nevertheless, the
Finally, we performed a meta-analysis fitting a fixed-effects model to verify
the results assessed using the random-effects model. The results showed a
significant difference between
To define the source of heterogeneity, we performed a sensitivity analysis
by removing studies one by one. The results indicated that studies performed
by Dong and Du (2010) on the Lubei White breed and by Feng et al. (2014) and
Moghadaszadeh et al. (2015) influenced overall results of the meta-analysis by
increasing the
In conclusion, the meta-analysis we have conducted has some advantages: (1) the data used in this meta-analysis were collected from all studies
published in several languages; (2) for our meta-analysis study we have used
four different genetic models to investigate association between
c.963A
Ultimately, the findings of the present meta-analysis study showed
significant association between c.963A
The original data from the paper are available from the corresponding author upon reasonable request.
All authors made substantial contributions to each step of the experimental procedure and paper preparation. EZ and JR searched in all journals and collected the data. MR performed data analysis and sorted the data. AR resolved all conflicts and disagreements for inclusion and exclusion of studies. Finally, JT revised the paper and prepared it for submitting. All of the authors read and accepted the paper.
The contact author has declared that none of the authors has any competing interests.
We used data from other papers, and no ethical statement is required.
Publisher’s note: Copernicus Publications remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
The authors wish to acknowledge and thank all the authors that published their papers around the world and let us use them for our study.
This paper was edited by Steffen Maak and reviewed by Xianyong Lan and one anonymous referee.