Harmful alleles can be under balancing selection due to an interplay of artificial selection for the variant in heterozygotes and purifying selection against the variant in homozygotes. These pleiotropic variants can remain at moderate to high frequency expressing an advantage for favorable traits in heterozygotes, while harmful in homozygotes. The impact on the population and selection strength depends on the consequence of the variant both in heterozygotes and homozygotes. The deleterious phenotype expressed in homozygotes can range from early lethality to a slightly lower fitness in the population. In this review, we explore a range of causative variants under balancing selection including loss-of-function variation (i.e., frameshift, stop-gained variants) and regulatory variation (affecting gene expression). We report that harmful alleles often affect orthologous genes in different species, often influencing analogous traits. The recent discoveries are mainly driven by the increasing genomic and phenotypic resources in livestock populations. However, the low frequency and sometimes subtle effects in homozygotes prevent accurate mapping of such pleiotropic variants, which requires novel strategies to discover. After discovery, the selection strategy for deleterious variants under balancing selection is under debate, as variants can contribute to the heterosis effect in crossbred animals in various livestock species, compensating for the loss in purebred animals. Nevertheless, gene-assisted selection is a useful tool to decrease the frequency of the harmful allele in the population, if desired. Together, this review marks various deleterious variants under balancing selection and describing the functional consequences at the molecular, phenotypic, and population level, providing a resource for further study.

Intermuscular bones (IBs) are slender linear bones embedded in muscle, which ossify from tendons through a process of intramembranous ossification, and only exist in basal teleosts. IBs are essential for fish swimming, but they present a choking risk during human consumption, especially in children, which can lead to commercial risks that have a negative impact on the aquaculture of these fish. In this review, we discuss the morphogenesis and functions of IBs, including their underlying molecular mechanisms, as well as the advantages and disadvantages of different methods for IB studies and techniques for breeding and generating IB-free fish lines. This review reveals that the many key genes involved in tendon development, osteoblast differentiation, and bone formation, e.g., scxa, msxC, sost, twist, bmps, and osterix, also play roles in IB development. Thus, this paper provides useful information for the breeding of new fish strains without IBs via genome editing and artificial selection.
肌间刺（intermuscular bones，IBs）是仅存在于低等硬骨鱼类肌肉中的细长的线形骨骼， 由肌腱组织通过膜内骨化形成。虽然肌间刺在鱼类游泳过程中发挥重要作用，但是在人类食用过程中会导致潜在的卡喉咙的风险，尤其不方便儿童的食用，这也进一步影响了水产业的经济效益。该文综合阐述了肌间刺的形态发生和功能、相关发育分子机制、肌间刺不同研究方法，以及用于培育无肌间刺鱼类品系的相关技术。该综述揭示了许多与肌间刺发育相关的关键基因，它们主要参与肌腱发育、成骨细胞分化和骨形成发育，如scxa、msxC、sost、twist、bmps和osterix基因。因此，该文对如何利用基因组编辑和人工选育等办法培育无肌间刺的鱼类品系提供了有价值的信息。.