{"created":"2023-06-19T07:18:13.041121+00:00","id":3466,"links":{},"metadata":{"_buckets":{"deposit":"6b23109c-e1d0-4e5a-8b1e-66f722781620"},"_deposit":{"created_by":4,"id":"3466","owners":[4],"pid":{"revision_id":0,"type":"depid","value":"3466"},"status":"published"},"_oai":{"id":"oai:az.repo.nii.ac.jp:00003466","sets":["370:193:374"]},"author_link":["16691","18485"],"item_10006_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2013-11-25"}]},"item_10006_degree_grantor_9":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"麻布大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"32701","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_10006_degree_name_8":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(学術)"}]},"item_10006_description_22":{"attribute_name":"Abstract","attribute_value_mlt":[{"subitem_description":"General introduction\nIn recent years, the business performance in Japanese pig industry have deteriorated by increasing production costs due to higher feed prices and imports of low price pork from abroad, and pig herd size in Japan which recorded 12 million heads in 1989 is a steadily decreasing every year. It is required the efficiency of pig productivity by improving of feeding and management technology, and breeding pigs that have superior genetic talent in order to stabilize the domestic pig production management. \nFor conducting improvements of breeding pigs, pure breed such as Landrace, Large White, or Duroc have been mainly used in Japan. The methods in breeding scheme are distinguished between open nucleus breeding system and closed nucleus breeding system. Open nucleus breeding system is the method conducted by the improvement of desired traits of the population with introducing genetic resources continuously from other populations, which is mainly performed in private breeders in Japan. On the other hands, closed nucleus breeding systems is uniquely developed in Japan, which is mainly performed in public breeders such as local governmental institute or National Agricultural Co-operative (ZEN-NOH). The closed nucleus breeding scheme is performed by repeating the selection superior pigs through about five generations in the isolated population, in which new genetic resources are not introduced from other populations. \nIn any case, the traits for improvement are mainly quantitative traits such as production traits, fertility traits, or meat quality, which are dominated by numerous polygenes that have complicated relationship. In modern breeding works, most genetic progress for quantitative traits in livestock has been performed by predicting the genetic value which is called an estimated breeding value that are calculated by means of statistical model such as BLUP (Best linear unbiased prediction) method. \nRecently, many approach that implicate genetic evaluation of individuals by not only phenotype-based method, but by gaining insight into the “black box” of quantitative traits with using molecular genetic information have been investigated in order to increase selection accuracy and decreasing generation intervals. Although many candidate genetic markers have been detected, the genetic makers that are available in the industry were very limited. The aims of this study were to evaluate genetic effect of genes that might affect productive traits in the Duroc population, and to establish the breeding scheme by adding genotype information. Duroc pigs used entirely in this study were from a line selected through five generations at Central Research Institute for Feed and Livestock ZEN-NOH (Hokkaido, Japan) from 2004 to 2010.\n\nCHAPTER 1. Breeding experiments on strain development in Duroc pigs\nThe Strain development with Duroc was performed through five generations to develop a line which has excellent production trait and meat quality to be used as terminal sire. Average daily weight gain (ADG), backfat thickness (BFT), and intramuscular fat content in the loin (IMF) were configured as improvement traits in this population. The pigs were selected mainly based on animal model BLUP of breeding value of each traits. Average phenotypic values of the ADG and BFT of boars at the fifth generation significant increased by 44g/day, 0.21cm compared with first generation, respectively. But phenotypic value of IMF decreased 0.31%. The each breeding value of ADG, BFT, and IMF at the fifth generation significantly increased by 82 g/day, 0.32cm, and 0.83% compared with those of the first generation, respectively. An average inbreeding coefficient and average relationship coefficient of selected pigs at fifth generation were 3.02%, 10.09%, respectively. And all selected pig at fifth generation had relationship each other. \n\nCHAPTER 2. Association of porcine beta 3-adrenergic receptor gene (ADRB3) gene with production traits in Duroc pigs\nAn insertion/deletion variant of a thymine base (T5 and T6) in exon 2 of porcine beta 3-adrenergic receptor (ADRB3) gene has been described. In the current study, we made an association study between the ADRB3 polymorphisms and production traits in 735 Duroc pigs. The allele frequencies for the T5 and T6 alleles in our study population were 0.567 and 0.433, respectively. Any associations were not detected between ADRB3 genotype and average daily weight gain during test period, or backfat thickness and intramuscular fat content in either sex. However the size of the loin eye muscle area (EMA) was significantly associated with ADRB3 genotypes in gilts. T6-homozygous gilts had a 2.5cm2 higher mean of EMA than T5-homozygous gilts. This association was not detected in males. In addition, a multiple traits animal model best linear unbiased predictor (BLUP) analysis revealed that the T6-homozygous genotype had positive effects on breeding value of EMA. Accordingly, we suggest that ADRB3 polymorphism has the potential to be an important genetic marker for prediction of EMA in Duroc pigs.\n\nCHAPTER 3. Association of porcine class 3 phosphoinositide-3-kinase (PIK3C3) gene with production traits in Duroc pigs\nA C↔T SNP on exon 24 of the porcine class 3 phosphoinositide - 3 - kinase (PIK3C3) gene is considered a possible genetic marker for selecting backfat (BF) thickness and carcass fat, although only one study has published results on its effects by performing experiments on a single resource family. In this chapter, we analyzed the association of this PIK3C3 polymorphism with production traits in our Duroc line in order to reveal the utility of this gene as a genetic marker. The C allele frequency at fourth generation was 75.2%, and significantly increased from second generation (63.5%). PIK3C3 polymorphism showed significant effects on ADG, BFT, IMF, and EMA, and the C alleles have increase effect on ADG, BFT, and IMF, and decrease effect on EMA. The predicted differences in traits between the homozygous pigs of the C and T alleles were 40 g/day for DG, 1.2 mm for BF, 0.44% for IMF, and 1.6 cm2 for EMA. Furthermore, the statistical models for estimating the breeding values of each trait had lower Akaike’s information criterion (AIC) values when adding PIK3C3 genotype information. We therefore confirmed that the c.2604C<T polymorphism in PIK3C3 has the potential to be a genetic marker for production traits in our Duroc line.\n\nCHAPTER 4. Association of porcine Vertnin(VRTN) gene with production traits in Duroc pigs\nVertebral number is related to body size in pigs, and many reports have suggested presence of an association between body length and meat production traits. Previous study revealed that variation in the vertebral number of Western breed (Duroc, Landrace, and Large white) is strongly associated with haplotype of Vertnin (VRTN) gene that is located on Sus scrofa chromosome 7. However, the relationship between Q and Wt haplotypes of VRTN gene and the production traits such as growth rate, fat deposition, or meat quality have not been investigated. In this chapter, we analyzed the association between the VRTN genotype and the production and body composition traits in Duroc pigs. The VRTN genotype was closely related to body length in a similar to previous studies, and the Q/Q genotype individuals (100.0 cm) were longer than individuals with the Wt/Q (99.5 cm) and Wt/Wt genotypes (98.9 cm). Intramuscular fat content (IMF) in the longissimus muscle was significantly associated with the VRTN genotype. The mean IMF of individuals with the wild-type genotype (Wt/Wt) (5.22) was greater than that of individuals with the Wt/Q (4.99) and Q/Q genotypes (4.79). In addition, the Wt allele had a positive effect on the IMF breeding value. No associations were observed between the VRTN genotype and other production traits. These results suggest VRTN has the potential to act as a genetic marker of IMF in Duroc population.\n\nCHAPTER 5. Evaluation of effects of multiple candidate genes (LEP, LEPR, MC4R, PIK3C3, and VRTN) on production traits in Duroc pigs\nNumerous studies have been detected the genetic marker for the improvement of traits. Although several dozen of candidate genes were detected as genetic marker might be related with backfat thickness, most study reported single marker effect only. Production traits such as average daily weight gain (ADG) or backfat thickness (BFT) are typical quantitative traits under the control of multiple genes. In this chapter, we evaluated single and combination effects of genetic variations of five candidate loci (LEP, LEPR, MC4R, PIK3C3, and VRTN) on four production traits (ADG, BFT, EMA, IMF) in 1414 Duroc pigs. Polymorphisms in LEPR, MC4R, and PIK3C3 had significant single gene effects on ADG and BFT. The additive genetic variance in ADG and BFT (16.99% and 22.51%, respectively) was explained by genetic effects of these three loci. No correlations were observed between the LEP genotype and production traits in this study. There were no epistatic effects between all selected combinations of loci pairs and analyzed traits, except for a pair of LEPR and PIK3C3. A marginally epistatic effect on EMA was detected between this loci pair, however, this effect did not reach statistical significance after FDR correction. These results suggested that LEPR, MC4R, PIK3C3, and VRTN may influence ADG and fat deposition independently of each other loci. Furthermore, we compared the fitness of the statistical models for predicting the breeding values that included multiple gene effects by Akaike’s information criterion (AIC) values. The models which included three genes effects (LEPR, MC4R, and PIK3C3) for ADG, four genes effects (LEPR, MC4R, PIK3C3, and VRTN ) for BFT, and two genes effects (LEPR and VRTN) for IMF as fixed effects showed the most favorable in this study, respectively. This study suggested that addition of multiple appropriate markers into mathematical model as fixed effect might be useful to predict individual genetic traits more accurately. \nGeneral discussion\nMost genetic improvements in Japanese pig industry are based on selection for economical traits in pure breed population such as Landrace, Large White, or Duroc. These traits are quantitative traits dominated by numerous polygenes that have respective little effect. Although several QTLs that may have relatively large effect were reported, it is much limited the proportion of genetic variance accounted for by those QTLs. Therefore, index selection method which is called MABLUP (Marker- Assisted BLUP) is expected to be the most advantageous for incorporating the marker information into genetic evaluation in practical breeding program to combine selection on the marker data with selection on the phenotype-based BV. It is because that can capture the all QTL and polygenic effect, which include those are not captured by the marker data. Furthermore, it is sufficient to utilize the LE marker (loci shows linkage equilibrium with the functional mutation in particular population) as the DNA marker, which segregates in specific population for increasing selection efficiency in the inbreeding such as Japanese closed nucleus breeding systems that have no genetic introduction from other populations except for base population. Present study in the Chapter 5 suggested that simultaneous addition of multiple appropriate markers might be useful to predict individual genetic traits more accurately. Thus, the present study suggested that the two step strategy lead the efficient implicating the strain development with using genetic marker, which is consisted by step 1; choosing the appropriate markers at early generation, and step 2; predicting individual genetic talent by phenotype based BLUP which include some marker effects as fixed effect. This study presented useful genetic maker information and the statistical methods for incorporating genetic marker effects into improvement pigs by closed nucleus breeding scheme.","subitem_description_type":"Other"}]},"item_10006_description_7":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"日本における種豚の育種改良は、一般的に純粋種の繁殖能力、産肉能力および、肉質などの経済形質を対象に行われている。種豚の改良手法は、開放型育種と閉鎖群育種に大別される。開放型育種は、基礎集団に随時外部から優良な個体を導入し短期間で能力の向上を図る手法で、主に国内外の民間種豚会社が用いる改良手法である。閉鎖群育種は、我が国独自に発展を遂げた改良手法で、群外から新たな個体の導入がない閉鎖集団内で交配を行い、後代の能力検定と選抜を、5～7世代にわたり継続する。これにより、遺伝的斉一性が高まり、個体間の能力差が小さい系統を作り出すことが可能となる。2つの改良手法ともに個体の選抜は、形質の表型値、環境効果および、家系血縁情報をもとにBLUP法を用いて算出した各個体の遺伝的能力（育種価）を用いて実施するのが一般的である。\n　近年、効率的な育種改良を行うために、形質と関連する遺伝子マーカーの開発が盛んに行われている。しかし、実際の種豚の改良に、遺伝子マーカーが活用されている例は、まだ少ない。これは、育種価に基づいた選抜改良に個々の遺伝子マーカー情報を反映する手法が十分に確立していないからである。特に、日本では重要な育種戦略である閉鎖群育種に対して、遺伝子マーカー情報を活用する方法は、これまで研究されていない。\n　本研究では、閉鎖群育種を用いて造成したデュロック種集団を対象に、産肉性や肉質などの経済形質に相関する遺伝子マーカーの探索を行った。さらに、遺伝子マーカー情報を、統計モデルに組み入れることで、選抜改良の指標となる育種価の推定精度がどのように変化するのかを検討し、実際の改良に遺伝子マーカー情報を活用する手法の開発と、その有用性を検証した。\n　本論文は5つの章で構成されており、第1章では、第2章以降の研究の基盤となるデュロック種集団の計測値に対する各種統計分析を実施した。第2章では、ADRB3遺伝子型多型と産肉形質との関連性解析、第3章ではPIK3C3遺伝子型多型と産肉形質の関連性解析、第4章では、VRTN遺伝子と産肉形質および体尺測定値との関連性解析を実施した。第5章では、第3章と第4章で解析した2つの遺伝子に、先行研究で形質との相関が報告されているLEP、LEPRおよびMC4R遺伝子を加えた、5つの遺伝子の組み合せ効果を考慮した統計モデルを考案し適合度を比較検討した。\n\n第１章　系統造成手法を用いたデュロック種集団の育種改良試験\n　1日平均増体重、背脂肪厚、および筋肉内脂肪割合を選抜形質をとし、5世代にわたって多形質アニマルモデルBLUP法により各形質の育種価を算出し、総合育種価、体型、家系をもとに個体の選抜を行なった。この系統造成の過程で測定した表現型値の変化に対して理論育種学的分析を行った。系統が完成した第5世代目を、第1世代と比較すると、1日平均増体重、背脂肪厚および、筋肉内脂肪割に対する育種価は、それぞれ82g/日、0.32cm、0.83%増加していた。また、第5世代における血縁係数は10.09%、近交係数では3.15%であり、全ての個体は、互いに血縁関係を有していた。\n\n第２章　デュロック種集団におけるブタADRB3遺伝子と産肉形質の関係\n　ADRB3遺伝子の変異は、ヒトにおいて成人型肥満と関連付けられている。ブタADRB3遺伝子には、エクソン2におけるチミン塩基の挿入／欠失による多型（T5型、T6型）が存在するが、形質への影響は不明であった。本章では第1章で詳説したデュロック種集団に含まれる735個体を用いてADRB3遺伝子多型と1日平均増体重、ロース芯面積、背脂肪厚および筋肉内脂肪割合との関連性を調査した。1日平均増体重、背脂肪厚、筋肉内脂肪割合においてはADRB3遺伝子型による差は見られなかった。しかし、雌においてロース芯面積とADRB3遺伝子型間に有意な相関が認められ、T6対立遺伝子にはロース芯面積を増加させる効果が認められた。さらに、多形質アニマルモデルBLUPで求めたロース芯面積の育種価とADRB3遺伝子型間にも有意な相関が検出された。以上の結果から、ADRB3遺伝子はデュロック種においてロース芯面積に対する遺伝子マーカーに成り得ることが示唆された。\n\n第３章　デュロック種集団におけるブタPIK3C3遺伝子と産肉形質との関係\n　PIK3C3遺伝子のエクソン24に存在するSNP（c.2604C>T）は、ブタの背脂肪厚と相関があるとの報告されているが、まだ十分な検証が行われていない。本章研究では、本第1章で詳説したデュロック種集団から739個体を用いてPIK3C3遺伝子の遺伝子型多型と産肉形質との関連性を調査した。その結果、1日平均増体重、背脂肪厚、ロース芯面積、および筋肉内脂肪割合においてPIK3C3遺伝子型による差が見られた。c.2604C対立遺伝子は、1日平均増体重、背脂肪厚、筋肉内脂肪割合を増加させ、 逆にロース芯面積を減少させる効果が認められた。PIK3C3遺伝子型の情報を固定効果とした数学モデルでは、遺伝子型の効果を含まないモデルよりもAIC値（赤池情報量基準）が小さくなり、モデルの適合度がよくなることが示された。本研究の結果からPIK3C3（c.2604C>T）遺伝子型多型は、デュロック種において産肉形質を改良するための有用な遺伝子マーカーに成り得ることが示唆された。\n\n第４章　デュロック種集団におけるブタVRTN遺伝子と産肉形質の関係\n　ランドレース種、デュロック種などの西洋品種の椎骨数の多様性は、VRTN遺伝子によって支配されていることが明らかになっている。西洋品種のVRTN遺伝子には、複数の多型から構成される増大型と野生型の2つのハプロタイプが存在する。椎骨数は枝肉形状と強く相関があるものの、VRTN遺伝子と発育、産肉形質との関連性は、明らかになっていない。本章では第1章で詳説したデュロック種集団から1414個体を用いてVRTN遺伝子の遺伝子型と産肉形質及び体尺測定値との関連性について調査した。その結果、本研究で用いたデュロック種集団でも、以前の研究と同様にVRTN遺伝子が体長と密接に関連することが確認された。さらにロース中の筋肉内脂肪割合とVRTN遺伝子型間にも有意な関連が認められ、野生型は増大型よりも筋肉内脂肪割合が高いことが明らかとなった。本章の結果から、デュロック種においてVRTN遺伝子の多型は、椎骨数だけではなく、筋肉内脂肪割合を改良するための遺伝子マーカーにもなり得ることが示された。\n\n第５章　デュロック種集団における複数の遺伝子（LEP, LEPR, MC4R, PIK3C3, VRTN ）と産肉形質の関係およびモデルの適合度の評価\n　これまでにブタの産肉形質に関連する多くの遺伝子マーカーが報告されている。背脂肪厚などの量的形質は、数多くの遺伝子が関与しているため、複数の遺伝子マーカーを組み合わせて利用することが、育種改良において有効であると思われる。しかしながら、これまでに複数の遺伝子マーカーの組合せ効果について検証されている報告はほとんどない。本章では、第1章で詳説したデュロック種集団から1414個体を用いて第3章で産肉形質との相関が検出されたPIK3C3遺伝子、第4章で筋肉内脂肪割合との相関が検出されたVRTN遺伝子に、先行研究において産肉形質との関連性が報告されている3つの遺伝子（LEP, LEPR, MC4R ）を加えた合計5つの遺伝子の組み合わせ効果を解析した。さらに、各遺伝子の効果を組み合せたモデルについてAICを用いて適合度の比較を行った。その結果、1日平均増体重では、3遺伝子（LEPR, MC4R, PIK3C3 ）、背脂肪厚では4遺伝子（MC4R, LEPR, PIK3C3, VRTN ）、筋肉内脂肪割合では2遺伝子（LEPR, VRTN ）の効果を固定効果としてモデルに含めた時に、最も適合度が高くなった。すなわち、本研究の結果により、複数の遺伝子の効果を、それぞれ固定効果として数学モデルに適応すると、育種価の推定精度が向上することが示された。\n\n総合考察\n　本研究では、形質と相関関係にある複数の遺伝子マーカーの効果を同時に母数効果としたモデルの適合度が、遺伝子マーカーの効果を考慮しない従来のモデルに比べて高くなることが示された。したがって、外部からの個体の導入がない閉鎖群育種集団の改良に遺伝子の効果を利用する場合、初期世代において形質と相関があるマーカーを検索し、従来のBLUP法を用いたモデルに、それらを母数効果として組み込めばよいことが明らかとなった。\n　以上、本研究で得られた多くの知見によって、閉鎖群育種による種豚改良に対して、有効な遺伝子マーカーと遺伝子情報を効率的に活用するための統計手法を開発することができた。","subitem_description_type":"Abstract"}]},"item_10006_dissertation_number_12":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"乙第4号"}]},"item_10006_version_type_18":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open 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