lncRNA調(diào)控畜禽抗病力性狀研究進(jìn)展

楊金艷，劉雪琴，文天琦，孫愉洪，俞英

綜 述

lncRNA調(diào)控畜禽抗病力性狀研究進(jìn)展

楊金艷1,2，劉雪琴1,2，文天琦1，孫愉洪1，俞英1

1. 中國農(nóng)業(yè)大學(xué)動物科學(xué)技術(shù)學(xué)院，北京 100193 2. 云南農(nóng)業(yè)大學(xué)動物科學(xué)技術(shù)學(xué)院，昆明 650201

長鏈非編碼RNA (long non-coding RNA, lncRNA)是一類長度大于200個核苷酸的非編碼RNA分子。lncRNA雖然不具備蛋白編碼能力，但可通過轉(zhuǎn)錄調(diào)控、轉(zhuǎn)錄后調(diào)控及表觀遺傳修飾調(diào)控等方式影響基因的表達(dá)，進(jìn)而影響性狀的表型。在現(xiàn)代畜牧業(yè)生產(chǎn)中，除提高生長發(fā)育和產(chǎn)量性狀外，研究免疫因子、細(xì)胞因子等抗病力相關(guān)指標(biāo)及性狀的調(diào)控機(jī)制，對提高和改善畜禽的健康、福利及公共衛(wèi)生尤為重要。近年來，利用lncRNA研究雞()、豬()、牛()等重要畜禽的抗病力性狀的調(diào)控機(jī)制取得了一定進(jìn)展，為將表觀遺傳標(biāo)記應(yīng)用于動物抗病遺傳育種打下了一定的基礎(chǔ)。本文介紹了lncRNA的生物學(xué)功能和產(chǎn)生機(jī)制，著重闡述了lncRNA對畜禽抗病力性狀的調(diào)控作用及研究進(jìn)展，以期為lncRNA在畜禽抗病遺傳育種方面的研究及應(yīng)用提供科學(xué)依據(jù)。

lncRNA；畜禽；抗病力性狀

如何提升高產(chǎn)畜禽的抗病力水平，是目前影響畜牧業(yè)穩(wěn)健發(fā)展的重要科學(xué)問題之一。畜禽抗病力與大部分重要經(jīng)濟(jì)性狀呈一定程度的負(fù)相關(guān)。

抗病力主要分廣義抗病力和狹義抗病力兩類。廣義抗病力指抗逆性或抗性，包括機(jī)體對疾病的抵抗力，以及對不良?xì)夂虻哪褪芰斑m應(yīng)性等[1]。狹義抗病力是指畜禽通過抑制感染，降低病原體的增殖速度[2]，不僅涉及機(jī)體對某種特殊病原體的抵抗力，也與機(jī)體-病原-環(huán)境互作密切相關(guān)[3]。

畜禽的大部分抗病力性狀，如一般性或特殊性抗體水平等屬于中低遺傳力性狀，除遺傳因素外，更容易受病原、環(huán)境及表觀遺傳修飾的影響。表觀遺傳修飾是機(jī)體與環(huán)境(包括病原體)互作的重要調(diào)控機(jī)制之一，主要包括DNA甲基化、組蛋白修飾以及非編碼RNA (non-coding RNA, ncRNA)等。其中長鏈非編碼RNA (long non-coding RNA, lncRNA)是ncRNA的重要類型之一，可通過染色質(zhì)水平、轉(zhuǎn)錄前和轉(zhuǎn)錄后水平調(diào)控基因的表達(dá)[4～6]。近年來，國內(nèi)外的研究人員對宿主lncRNA的調(diào)控機(jī)制及功能關(guān)注度日益增加，研究人員開辟了從lncRNA角度研究畜禽疾病發(fā)生發(fā)展及抗病力水平的新途徑，發(fā)現(xiàn)lncRNA可以通過參與炎癥反應(yīng)、免疫應(yīng)答、細(xì)胞周期等生物學(xué)通路，調(diào)控相關(guān)基因的表達(dá)水平，進(jìn)而影響畜禽的抗病能力。本文主要綜述了lncRNA的生物學(xué)功能及作用機(jī)制，以及在雞()、豬()、牛()等主要畜禽抗病力研究領(lǐng)域的新進(jìn)展和研究策略。

1 lncRNA概述

對lncRNA的研究是一個由表及里，不斷深入細(xì)化的過程。在20世紀(jì)90年代之前，lncRNA被科學(xué)界普遍認(rèn)為是轉(zhuǎn)錄的副產(chǎn)物，不具有編碼能力，是無用的“垃圾”。20世紀(jì)90年代，有研究發(fā)現(xiàn)lncRNA能夠參與調(diào)控表觀遺傳過程，如H19和XIST等[7,8]，lncRNA的功能開始被研究者所關(guān)注。2002年，Okazaki等[9]證實(shí)lncRNA為轉(zhuǎn)錄組的重要組成部分，初步提出了lncRNA的概念。

lncRNA是一類由RNA聚合酶II轉(zhuǎn)錄產(chǎn)生、缺乏開放閱讀框架且長度大于200 nt的轉(zhuǎn)錄物[10]。雖然lncRNA不具有蛋白質(zhì)編碼能力，但分子結(jié)構(gòu)和mRNA相似，具有5′鳥苷帽和3′聚腺苷殘基末端，因此又被稱為“與mRNA類似的非編碼RNA”(mRNA-like non-coding RNA, mlncRNA)[11]。依據(jù)lncRNA相對于蛋白質(zhì)編碼基因的位置，可將lncRNA分為5類[12]：正義lncRNA、反義lncRNA、雙向lncRNA、內(nèi)含子lncRNA和基因間lncRNA。

在生物體中，lncRNA存在4種產(chǎn)生模式[12]：(1)蛋白質(zhì)編碼基因突變導(dǎo)致框架結(jié)構(gòu)斷裂，從而產(chǎn)生lncRNA (圖1A)；(2)同一序列復(fù)制兩次，使相鄰的非編碼RNA產(chǎn)生重復(fù)序列(圖1B)；(3)轉(zhuǎn)座原件序列插入之后，可產(chǎn)生具有功能的lncRNA (圖1C)；(4)非編碼基因通過逆轉(zhuǎn)錄復(fù)制，也會產(chǎn)生lncRNA (圖1D)。

圖1 產(chǎn)生lncRNA的主要模式[12]

A：蛋白質(zhì)編碼基因的閱讀框發(fā)生斷裂，產(chǎn)生lncRNA XIST；B：lncRNA Kcnq1ot1的5?區(qū)觀察到的重復(fù)序列；C：lncRNA BC1和 lncRNA BC200來源于轉(zhuǎn)座因子的插入；D：lncRNA AK019616和lncRNA NEAT2由逆轉(zhuǎn)錄復(fù)制產(chǎn)生。圖根據(jù)文獻(xiàn)[12]修改繪制。

lncRNA可以通過順式(，臨近基因)和反式(，遠(yuǎn)距離基因)兩種方式調(diào)控細(xì)胞中蛋白編碼基因的表達(dá)。近年來，lncRNA的研究不斷深入，其生物學(xué)功能研究從最初的基因組印記、染色質(zhì)重塑，深入至細(xì)胞凋亡周期調(diào)控、mRNA的降解、剪接調(diào)控和翻譯調(diào)控等[13～23](表1)。

表1 典型lncRNAs的作用機(jī)制及關(guān)鍵靶標(biāo)

2 畜禽抗病力性狀相關(guān)lncRNAs的篩選和鑒定

在畜禽養(yǎng)殖過程中，動物體若感染細(xì)菌或病毒等病原微生物，將引起各類流行性疾病或傳染性疾病的發(fā)生，導(dǎo)致巨大損失并威脅人類健康。近年來，研究人員探究了病原-lncRNA-宿主相互作用的分子機(jī)制，鑒定和挖掘出了一批關(guān)鍵的lncRNAs，為畜禽疾病的診斷、防治和抗病遺傳育種提供了重要的分子生物學(xué)標(biāo)記(表2)。

2.1 雞抗病力性狀相關(guān)lncRNAs標(biāo)記

家禽養(yǎng)殖過程中的常見腫瘤性疾病主要包括禽白血病(avian leucosis, AL)和馬立克氏病(Marek's disease, MD)，分別由禽白血病病毒(avian leukosis virus, ALV)及馬立克氏病毒(Marek’s disease virus, MDV)引起。這兩種病毒性腫瘤疾病在不同雞群中的發(fā)病率約為15.4%～61%[50,51]，雙重感染率高達(dá)21.92%[52]。J亞型禽白血病病毒(avian leukosis virus subgroup J, ALV-J)感染可引起雞的腫瘤性疾病，并導(dǎo)致免疫抑制。有研究表明，雞巨噬細(xì)胞(monocyte-derived macrophages, MDMs)感染ALV-J 3小時后，128個lncRNAs和15個miRNAs差異表達(dá)；感染36小時后，僅發(fā)現(xiàn)30個lncRNAs和8個miRNAs差異表達(dá)[24]，這說明lncRNA在ALV感染早期比后期更加活躍。感染3小時后的MDMs細(xì)胞中，XLOC_672329、ALDBGALG0000001429、XLOC_016500等差異表達(dá)的lncRNAs 可以上調(diào)免疫相關(guān)基因、和的表達(dá)水平。與ALV-J未感染組雞相比，感染組雞中差異表達(dá)lncRNAs的靶基因主要富集于MAP激酶活性、炎癥反應(yīng)等GO條目以及VEGF信號通路、基礎(chǔ)轉(zhuǎn)錄因子等生物學(xué)通路[25]。ALV-J感染組中差異表達(dá)的lncRNA TCONS_00060450可以作為潛在的ceRNA，調(diào)控關(guān)鍵基因的表達(dá)水平。不僅是一種重要的轉(zhuǎn)錄調(diào)控因子，也可作為腫瘤抑制基因[53]，異常表達(dá)的會誘發(fā)淋巴瘤及惡性腫瘤發(fā)生，影響馬立克氏腫瘤細(xì)胞系MSB1的增殖、遷移和侵襲[54]，但及相關(guān)lncRNAs的具體調(diào)控機(jī)制還需要進(jìn)一步驗(yàn)證。

雞MD相關(guān)報(bào)道中，F(xiàn)igueroa等[26]在馬立克氏病毒GaHV-2 (也稱MDV-1)基因組的TRL/IRL(long terminal repeat/ long internal repeats) 區(qū)域，發(fā)現(xiàn)一個長7.5 kb的lncRNA——ERL lncRNA (edited repeat- long, long non-coding RNA)。ERL lncRNA在GaHV-2病毒感染和再激活的裂解期和潛伏期均表達(dá)，在裂解期被過度編輯(hyperediting)，發(fā)生A-to-G事件(鳥嘌呤替代腺嘌呤)，該過程與干擾素誘導(dǎo)的基因的過表達(dá)有關(guān)。長基因間非編碼RNA (long intergenic non-coding RNAs, lincRNAs)是一種從編碼基因之間的DNA序列轉(zhuǎn)錄而來的lncRNA，lincRNAs的異常表達(dá)與各種類型的癌癥和神經(jīng)系統(tǒng)疾病有關(guān)[55]。在雞中已發(fā)現(xiàn)2個lincRNAs (linc- GALMD3和linc-stab1)能夠參與調(diào)控MD相關(guān)的免疫過程[27,28]。linc-GALMD3位于雞第4條染色體的兩個蛋白編碼基因之間，可以順式調(diào)控其下游基因的表達(dá)[27]，同時反式調(diào)控MDV感染細(xì)胞中其他基因的表達(dá)，如、等已有研究證實(shí)，下調(diào)將會導(dǎo)致雞后晶狀體角膜營養(yǎng)不良[56]，誘發(fā)雞虹膜發(fā)生病變。因此，linc-GALMD3被認(rèn)為是關(guān)鍵的調(diào)控因子，作為候選的表觀遺傳標(biāo)記物，用于MD的預(yù)防和診斷。此外，linc-stab1作為另一關(guān)鍵lincRNA，僅在MDV感染潛伏期的MDV抗性雞品系6中高表達(dá)，其表達(dá)水平與其鄰近的蛋白編碼基因的表達(dá)水平呈較強(qiáng)的正相關(guān)[28]，說明linc-satb1可能通過激活基因表達(dá)來發(fā)揮其抗MDV功能[57]。

2.2 豬抗病力性狀相關(guān)lncRNA標(biāo)記

在細(xì)菌感染引起的仔豬腸道炎癥反應(yīng)中，產(chǎn)氣莢膜梭菌()作為一種食源性人豬共患病病原體[58]，可通過產(chǎn)生α腸毒素、β腸毒素來激活免疫和炎癥相關(guān)的信號通路，增強(qiáng)靶細(xì)胞的毒性并誘導(dǎo)超氧化物的產(chǎn)生[59～61]。lncRNA失調(diào)將會誘導(dǎo)免疫相關(guān)基因表達(dá)，進(jìn)而影響炎性因子和促炎性細(xì)胞因子的表達(dá)[62]，如上調(diào)LNC_001066可以顯著上調(diào)產(chǎn)氣莢膜梭菌感染相關(guān)基因(、、)的表達(dá)水平[30]。同時，這些免疫相關(guān)基因的差異表達(dá)將會影響入侵過程中仔豬的耐藥性和易感性[63]。此外，研究人員還對仔豬感染后，參與免疫應(yīng)答lncRNA的表達(dá)模式和生物學(xué)功能進(jìn)行了深入探索。例如，有研究發(fā)現(xiàn)4個lncRNAs (ENSSSCT00000032859、ENSSSCT-00000018610、LNC_001066和LNC_001186)在抗性組(resistance groups, IR)及易感組(susceptibility groups, IS)中表達(dá)水平存在顯著差異[30]。而差異表達(dá)lncRNAs的靶向基因在ABC轉(zhuǎn)運(yùn)蛋白信號轉(zhuǎn)導(dǎo)、MAPK、趨化因子信號和toll樣受體等信號通路顯著富集，表明這些lncRNAs能夠參與調(diào)節(jié)仔豬感染期間的免疫反應(yīng)和抗性[31,32,64]。腸毒素大腸桿菌(enterotoxigenic, ETEC)作為另一種致命性腸道病原菌，導(dǎo)致56.2%的仔豬腹瀉和24.7%死亡病例[65]。Augustino等[33]全面分析了ETEC感染仔豬小腸上皮細(xì)胞的lncRNA和mRNA表達(dá)譜，結(jié)果顯示，LOC102157546和XLOC_025930這兩個關(guān)鍵lncRNAs參與 cGMP-PKG信號通路，調(diào)控3個黏附表型相關(guān)基因(、、)的表達(dá)水平，從而影響ETEC-F4ac的黏附表型。

表2 畜禽主要抗病性狀相關(guān)lncRNAs及其靶基因

在病毒引起的豬炎癥反應(yīng)與免疫反應(yīng)中，豬繁殖與呼吸綜合征是一種由豬繁殖與呼吸綜合征病毒(porcine reproductive and respiratory syndrome virus, PRRSV)引起的具有高傳染性的急性傳染病[66,67]。PRRSV表現(xiàn)出嚴(yán)格的細(xì)胞嗜性，主要靶細(xì)胞為豬肺泡巨噬細(xì)胞(pig alveolar macrophage, PAM)[68]。在PAMs被PPRSV感染的不同時間點(diǎn)，均可發(fā)現(xiàn)lncRNA表達(dá)譜發(fā)生顯著變化[69]。PRRSV感染PAMs 9個小時后，環(huán)氧合酶-2(COX-2)臨近的lncRNAXR_297549.1表達(dá)量顯著下調(diào)，lncRNA XR_297549.1能夠順式和反式調(diào)控免疫相關(guān)基因的表達(dá)水平[36]。另一研究推測[37]，PAMs中TCONS_00054158表達(dá)上調(diào)可能是豬被RNA病毒感染的共同特征，該lncRNA通過上調(diào)的表達(dá)水平，引發(fā)PRRSV感染過程中的細(xì)胞凋亡。上述研究為進(jìn)一步揭示lncRNA調(diào)控豬細(xì)菌病和病毒病的免疫應(yīng)答機(jī)制提供了理論基礎(chǔ)。

2.3 ?？共×π誀钕嚓P(guān)的lncRNA標(biāo)記

乳房炎是奶牛最常見的疾病之一，主要由宿主、病原體和環(huán)境因素相互作用引起，其中細(xì)菌感染是引起奶牛乳房炎的主要原因。大腸桿菌)、金黃色葡萄球菌()和牛分枝桿菌()能夠在乳腺組織中快速增殖、黏附并引起炎癥，是牛臨床和隱性乳房炎的主要傳染性病原體[70～72]。同時，宿主的免疫相關(guān)信號通路在對抗乳房炎時發(fā)揮重要的調(diào)控作用，例如NF-κB、MAPK、TLR和JAK-STAT等信號通路[73～76]。以大腸桿菌為主要致病菌的奶牛乳房炎中，脂多糖(lipopolysaccharide, LPS)是主要的毒力因子。LPS通過改變?nèi)橄偕掀ぜ?xì)胞緊密連接(tight junctions, TJs)的蛋白亞型來破壞血乳屏障[77]。有研究發(fā)現(xiàn)，在LPS誘發(fā)炎癥的組織中，lncRNA H19 (H19)的表達(dá)水平顯著上調(diào)。H19能夠促進(jìn)、、、等炎癥因子分泌，同時激活NF-κB通路，促進(jìn)與β-酪蛋白和緊密連接相關(guān)蛋白的表達(dá)水平，維持乳腺屏障的完整以防止乳汁成分從乳腺腺泡滲入血清[39]。以金黃色葡萄球菌或大腸桿菌為致病原的乳房炎中，lncRNA XIST (XIST)在MAC-T中表達(dá)水平顯著上調(diào)，XIST通過抑制NF-κB信號通路的激活，阻止炎性細(xì)胞因子的產(chǎn)生，并降低NLRP3炎癥小體的表達(dá)；同時，XIST可以通過負(fù)反饋回路來調(diào)控NF-κB/NLRP3炎癥小體通路，從而介導(dǎo)炎癥過程[40]。此外，以牛分枝桿菌為致病原的奶牛乳房炎中，牛分枝桿菌通過和基因激活NF-κB通路，增加IL-1β細(xì)胞因子的產(chǎn)生[78]。Ozdemir等[41]研究確定了與和基因顯著相關(guān)的lncRNAs (ALDBBTAT0000007617和ALDBBTAT0000006520等)，這些lncRNAs通過NF-κB和PI3K-Akt通路共同調(diào)控牛乳腺組織對牛分枝桿菌感染的免疫應(yīng)答。

在養(yǎng)殖過程中，若奶牛感染病毒性腹瀉病毒(bovine viral diarrhea virus, BVDV)，其消化系統(tǒng)會受到嚴(yán)重影響，并出現(xiàn)持續(xù)性腹瀉和腸炎[79]。BVDV感染牛腎細(xì)胞(Madin-darby bovine kidney cells, MDBK)后，隨著病毒在細(xì)胞中的復(fù)制，越來越多的基因被激活并參與免疫應(yīng)答，同時參與調(diào)控的lncRNAs數(shù)量也顯著增多[42]。BVDV感染過程中，MDBK中差異表達(dá)的lncRNAs可以靶向調(diào)控等自噬相關(guān)基因[42,43]。除了BVDV，奶牛在感染副結(jié)核分枝桿菌后，同樣也會出現(xiàn)周期性、頑固性腹瀉癥狀[80]。副結(jié)核分枝桿菌為牛副結(jié)核病的主要病原體，Gupta等[44]發(fā)現(xiàn)，由副結(jié)核分枝桿菌誘導(dǎo)的牛副結(jié)核病中，lncRNA (XLOC_ 033995)能夠調(diào)控其臨近的炎癥信號因子的表達(dá)水平，并通過參與NF-κB、細(xì)胞器裂變等免疫應(yīng)答相關(guān)的通路，影響巨噬細(xì)胞對感染的炎癥反應(yīng)進(jìn)程，最終調(diào)控牛副結(jié)核病的發(fā)病進(jìn)程。

以上研究結(jié)果提示，lncRNA可通過作用于關(guān)鍵靶基因，參與抗病相關(guān)基因所在的生物學(xué)通路，調(diào)控奶牛乳房炎、病毒性腹瀉等疾病的發(fā)展進(jìn)程。這些研究結(jié)果為奶牛疾病發(fā)生的生物標(biāo)記物挖掘以及奶?？共∧芰Φ奶嵘峁┝诵碌乃悸?。

2.4 羊抗病力性狀相關(guān)的lncRNA標(biāo)記

在羊中高發(fā)的羊寄生蟲疾病(肝片吸蟲病、肺絲蟲病、鉤蟲病)以及腐蹄病等常見疾病與lncRNA關(guān)系的研究較少。已有的研究中，Jin等[47]利用大腸桿菌F17菌株飼喂湖羊，并鑒定了對大腸桿菌F17有拮抗或敏感反應(yīng)個體的lncRNA表達(dá)情況，確定了lncRNAs與等6個基因共表達(dá)。鑒于的缺失會導(dǎo)致B淋巴細(xì)胞硬度降低，進(jìn)而影響B(tài)淋巴細(xì)胞的細(xì)胞黏附、增殖、吞噬和內(nèi)吞作用[81]，揭示lncRNA對大腸桿菌F17引起的綿羊腹瀉具有一定的調(diào)控作用。

3 結(jié)語與展望

隨著分子生物學(xué)技術(shù)的發(fā)展和不同物種轉(zhuǎn)錄組數(shù)據(jù)的積累，lncRNA從最初被認(rèn)為是轉(zhuǎn)錄的“副產(chǎn)物”，到后來被證實(shí)能夠參與調(diào)控人類及動物的多種關(guān)鍵生物學(xué)過程。如今越來越多的研究發(fā)現(xiàn)，lncRNA可作為豬、雞、牛等重要畜禽的抗病相關(guān)性狀的潛在分子標(biāo)記物，用于疾病的診斷及治療；同時，lncRNA靶向的基因有望作為畜禽傳染性疾病抗性相關(guān)的遺傳標(biāo)記，應(yīng)用于畜禽抗病個體的選擇。

然而，對于lncRNA的研究仍然面臨一些亟待解決的問題。如，與人類和小鼠等模式動物相比，畜禽的生物數(shù)據(jù)庫中保存的lncRNA轉(zhuǎn)錄本數(shù)量相對較少且注釋信息不完善。因此，未來需進(jìn)一步完善畜禽基因組lncRNA的注釋信息。此外，lncRNA的二級和三級結(jié)構(gòu)的保守性較高，且二級結(jié)構(gòu)中還存在許多未知的“功能性模塊”，增加了lncRNA在畜禽抗病育種中的研究難度?？梢灶A(yù)見的是，深入探究畜禽抗病相關(guān)的lncRNA分子遺傳標(biāo)記物，能夠?yàn)樾笄莸目共∵z傳育種提供更加準(zhǔn)確的科學(xué)數(shù)據(jù)。

致謝：

感謝中國農(nóng)業(yè)大學(xué)動物科學(xué)技術(shù)學(xué)院米思遠(yuǎn)、唐永杰、劉雪琴、史源鈞對本文的修改。

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Progress on lncRNA regulated disease resistance traits in domesticated animals

Jinyan Yang1,2, Xueqin Liu1,2, Tianqi Wen1, Yuhong Sun1, Ying Yu1

Long non-coding RNA (lncRNA) is a class of non-coding RNAs with a length greater than 200 nucleotides. Although lncRNAs do not have any protein coding capability, they can affect the phenotypes of traits by influencing gene expression through transcriptional regulation, post-transcriptional regulation, and epigenetic modification. In modern animal husbandry production, besides increasing growth and yield traits, investigations on the regulation mechanisms of immune factors, cytokines and other disease resistance-related indicators and traits are particularly important for improving the health and welfare of domesticated animals as well as public health. In recent years, researchers have made significant progress in understanding the regulatory mechanisms of lncRNA on the disease resistance traits of chickens (), pigs (), cattle (and other important domesticated animals, thereby laying the basic foundation for the translational application of epigenetic markers in breeding of animals with disease resistance. In this review, we briefly introduce the biological functions and the origins of lncRNAs, then focus on the research progress on the regulatory effects of lncRNAs on disease resistance traits of domesticated animals, and thus providing the scientific basis for the research of lncRNA and its application in the breeding of disease-resistant animals.

lncRNA; domesticated animals; disease-resistance traits

2021-01-10;

2021-06-16

國家自然科學(xué)基金項(xiàng)目(編號：31961143009，31272420)，北京市自然科學(xué)基金項(xiàng)目(編號：6182021)，北京市奶牛產(chǎn)業(yè)創(chuàng)新團(tuán)隊(duì)項(xiàng)目(編號：BAIC06)和國家奶牛產(chǎn)業(yè)技術(shù)體系項(xiàng)目(編號：CARS-36)資助[Supported by the National Natural Science Foundation of China (Nos.31961143009, 31272420), the Beijing Natural Science Foundation (No. 6182021), the Beijing Dairy Industry Innovation Team (No. BAIC06) and the National Dairy Industry Technology System Project (No. CARS-36)]

楊金艷，本科生，專業(yè)方向：動物科學(xué)。E-mail: cauyangjinyan@163.com

劉雪琴，在讀博士研究生，研究方向：動物分子數(shù)量遺傳學(xué)。E-mail: cauliuxueqin@163.com

楊金艷和劉雪琴并列第一作者。

俞英，博士，教授，博士生導(dǎo)師，研究方向：動物抗病遺傳育種及表觀遺傳調(diào)控機(jī)理。E-mail: yuying@cau.edu.cn

10.16288/j.yczz.20-230

2021/6/28 13:58:51

URI: https://kns.cnki.net/kcms/detail/11.1913.R.20210628.1047.002.html

(責(zé)任編委: 李明洲)