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OFA指導手冊~如何使用健康資料庫與實行選擇性繁殖 <遺傳學> 

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OFA指導手冊~如何使用健康資料庫與實行選擇性繁殖 <遺傳學>

文章泡泡拔 » 2006-08-21, 13:55

The use of health databases and selective breeding (如何使用健康資料庫與實行選擇性繁殖)

這是OFA在2006年最新版的指導手冊,裡面有很多統整性的概念,但是全部有81頁,我會盡力翻,希望暑假結束前可以把CHD的部份完成!
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文章泡泡拔 » 2006-08-21, 13:58

Introduction(簡介)
Breeders have an inherent responsibility to protect the comfort and
well-being of the animals they produce, yet the dog and cat owning
public spends hundreds of millions of dollars each year on
diagnosis and treatment of genetic diseases. These factors justify placing
continued emphasis on prevention of these diseases. Responsible breeders
and the more progressive breed clubs are, and have been, responding
to the challenge of improving the genetic health of our companions
through better breeding practices.

The Orthopedic Foundation for Animals, Inc., (OFA) is a private
non-profit foundation which formed a voluntary dysplasia control database
in 1966 with the following objectives:

1. To collate and disseminate information concerning orthopedic and
genetic diseases of animals.
2. To advise, encourage and establish control programs to lower the
incidence of orthopedic and genetic diseases.
3. To encourage and finance research in orthopedic and genetic disease
in animals.
4. To receive funds and make grants to carry out these objectives.

The OFA’s voluntary databases serve all breeds of dogs and cats and
have the world’s largest all-breed data bank on radiographic evaluations
of the hip and elbow. The testing methodology and the criteria for
evaluating the test results for each database were independently established
by veterinary scientists from the respective specialty areas. These
standards are accepted throughout the world and the results are used to
evaluate prevalence and progress in controlling the respective diseases
in the breeding population. The OFA serves as a central source of information
for breeders and owners based on the standards for evaluation,
and as a major source of funding for studies directed at animal wellness.
The purpose of this monograph is to assist the breeder, dog owner,
and veterinarian in accomplishing their goals by providing a summary of
information on the OFA databases, their methodology, and a reference
source for further study. Data on individual animals may be obtained at
www.offa.org. This data can be useful for the breeder to determine the
status of potential breeding animals and their family lines.

繁殖者有不可推卸的責任去保護自己所繁殖的動物,確保牠們享有舒適的生活與福利,不過我們每年還是花費了數百萬美元的社會成本,用在診斷與治療遺傳疾病上,基於這樣的原因,我們必須持續地重視這些遺傳疾病的預防。負責任的繁殖者與大部分發展中的犬種俱樂部,在過去與現在都願意面對這個挑戰 --- 藉由更好的繁殖規範來為我們忠實的朋友,增進遺傳上的健康。

OFA是一個私人非營利基金會,自願成立了發育障礙控制資料庫,並擁有以下幾個目標:

1. 驗證並宣導,關於動物骨骼關節與遺傳疾病的資訊
2. 建議、鼓勵並建立控管機制,以降低骨骼關節與遺傳疾病的發生率
3. 鼓勵並資助,關於動物骨骼關節與遺傳疾病的科學研究
4. 接受捐款並提供獎助金,去達成以上的目標

OFA資料庫提供了所有犬貓品種的相關資訊,並擁有全世界最大的資料銀行,以幫助髖關節與膝關節的放射線顯影評估。每個資料庫的檢查方法與檢查結果的評估標準,都是由來自不同地區的獸醫學科學家群,所獨立建構的。這些標準被全世界認同接受,而這些標準帶來的成果,則可以被用來評估這些標準在特定犬種族群,於疾病控制上的廣泛性與發展程度。OFA基於評估標準提供繁殖者與飼主一個中央資訊來源,同時也是動物健康研究的主要資金來源。

這一篇論文的目的,是想要提供 OFA資料庫的簡要資訊、方法學與鞤助進一步研究的參考文獻,以協助繁殖者、飼主與獸醫,去完成他們的目標。關於特定品種的資料,可以在www.offa.org取得,這些資料將對繁殖者非常有用,可以幫助他們評估繁殖動物的狀態與家族史


轉貼本文請註明出處:
犬髖關節狗友會(www.dogchd.net)泡泡拔 阮振維譯自www.offa.org
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文章泡泡拔 » 2006-08-21, 17:51

Genetics(遺傳學)

Inherited traits, desirable or not, are controlled by the genetic makeup
(genotype) of the individual dog or cat. The genotype is determined
by the genes received from the parents, one-half from the sire and
one-half from the dam. Most inherited traits in animals are polygenic.
Some examples are: conformation, type, size, longevity, disease resistance,
temperament, speed, milk and egg production, growth rate,
maturation and sexual maturity rate, and numerous inherited diseases.

Intuitively, it is recognized that these traits do not follow inheritance
patterns based on simple Mendelian genetics. Mendelian genetics usually
uses one pair of genes to explain basic genetic principles. For example,
assume that: 1) The color black is dominant to brown, 2) The black gene
is represented by B and the brown gene by b, and 3) a homozygous black
(BB) is mated with a brown (bb). All of the offspring will be black, but
will have the heterozygous Bb genotype. If two heterozygous blacks (Bb)
are mated, Mendelian genetics predicts the offspring are expected to be
three black (1 BB and 2 Bb) and one brown (bb). The ratio of 1:2:1 for the
genotypes is based on probability. If only a small number of offspring are
available from this type of mating, they may not fall within the ratio, but
larger numbers will produce the predicted results. In addition, the finding
of one brown offspring from the mating of black parents indicates that
both parents are carriers (heterozygous Bb) of the recessive brown gene.
In such a case, two out of three black offspring are also carriers, but until
they are bred it is uncertain which are the carriers. In the above example
of simple Mendelian genetics, the probable genotype of the parents can
be determined by examination of the progeny.

However, polygenic traits, such as most characteristics that breeders
are concerned with, are defined as those affected by multiple gene pairs.
An oversimplified example is two genes affecting the same trait. Assume
the mating of two dogs with genotypes of AaBb, where the dominant
alleles “A” and “B” are desirable. The expected genotypic outcome is
nine different genotypes with the following frequencies:

遺傳特徵,無論是否符合期望,都是由犬、貓個體的遺傳結構(基因型)來控制的。
而承襲自父母的基因即決定了基因型的種類,這些基因一半來自於父親,另一半則來自於母親。動物的大部分遺傳特徵都屬於多基因遺傳,有一些例子像是:結構型態、體型大小、壽命、抵抗力、脾氣、速度、泌乳、排卵、成長速率、成熟和性成熟速率,還有許多遺傳疾病。

直覺上,我們無法在孟德爾定律的前提下,藉由遺傳組態來辨認這些特徵。孟德爾定律通常只能用一組對偶基因,來解釋基礎的遺傳原則,例如:

假設 1) 黑色基因是顯性,棕色是隱性
2) 黑色基因以B代表,棕色基因以b代表
3) 帶有同型合子(BB)的種犬與帶有(bb)的種犬交配

結果所有的後代都會是黑色,但是會有異型合子(Bb)的基因型出現。如果兩隻帶有異型合子(Bb)的黑色種犬交配,依照孟德爾遺傳定律,我們將可以預測後代會是三黑(1 BB and 2 Bb)一棕(bb)。基因型1 : 2 : 1的比例是以機率原則推測出來的,如果只有少數的後代做為樣本,那麼也許結果不見得符合這個機率,但是若可以獲得較大量的後代樣本,結果就有可能符合預測。
值得一提的是,當兩隻黑色的種犬交配,若發現有一隻棕色後代,這表示父母都是異型合子(Bb)的帶原者,帶有隱性的棕色基因。在這樣的案例中,三隻黑色後代中會有兩隻帶有隱性基因,但除非牠們被用來繁殖,否則不會有人能確定他們是否為隱性基因帶原者。
在以上符合孟德爾定律的例子中,父母親可能帶有的基因型,是可以藉由檢驗其後帶的表現來推測的。

不過多基因遺傳特徵,像是大部分繁殖者所關心的特徵,是受到多組基因所共同影響控制的。舉一個簡化的例子,就是兩組基因影響了同一個表徵。假設兩隻帶有AaBa基因型的種犬交配,而我們想要的是顯性的“A”與“B”,那麼我們可以預期出現九種不同的基因型,伴隨著以下的頻率出現:
(genotypes:基因型,Frequency:頻率)


轉貼本文請註明出處:
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文章泡泡拔 » 2006-08-22, 21:07

轉貼本文請註明出處:
犬髖關節狗友會(www.dogchd.net)泡泡拔 阮振維譯自www.offa.org


續上篇~遺傳學

Only 25% of the progeny from this mating are expected to have the
same genotype for the trait as the parents. Some of the remaining progeny
will have a more desirable genotype (AABB, AABb, AaBB) while
others will have a less desirable genotype for the trait (Aabb, AAbb,
aaBB, aaBb, aabb). As the number of genes involved increases, the possible
combinations soar. The problem is further magnified if each gene
pair exerts a different degree of influence on a trait to produce an “additive” result.

It is currently impossible to precisely predict the specifi c
outcome of a particular mating with regard to polygenic (additive) traits
and probabilities can only be generally estimated.
However, animal geneticists have developed successful breeding
programs to improve milk production in cows, egg production in hens,
speed in horses, growth rate in food animals, etc. They use basic genetic
principles that have also been demonstrated effective in the dog. Some of
the following aspects of polygenic traits considered in arriving at these
principles include:

Polygenic traits have a range of manifestations from the most desirable to the least desirable characteristic under consideration.

For example, mating two dogs of ideal conformation can be expected
to result in a larger number of offspring with ideal conformation
when compared with offspring of a mating where one or both parents
have less than ideal conformation. However, both litters will
present a range of conformational characteristics.


Polygenic traits are influenced by environmental factors which
may minimize or maximize genetic potential.

For example, a horse with a respiratory infection will not be able
to achieve its genetic speed capability, or a cow on a starvation diet
will not produce milk to its full genetic potential.

(接上表)在這一次的交配中,只有25%的後代會符合我們的預期,和種犬帶有相同的基因型(AaBb:4/16)。其餘的後代會有一部份帶有更多我們想要的顯性基因(AABB, AABb, AaBB),一部分則會帶有我們不期望見到基因型(Aabb, AAbb,aaBB, aaBb, aabb),而出現非預期中的遺傳特徵。

以上經由簡化過的例子,其遺傳結果已經顯得有點複雜,若影響同一個性狀的基因數目增加了,那麼可能出現的基因型排列組合,也會大大地增加。而這個問題還會變得更複雜,如果每組基因對性狀的影響程度不同,就會造成“加成效應”的結果。

以我們現今的能力,對於我們關心的多基因遺傳性狀,是不可能精準地預測“特定的交配會產生何種特定的後果”,只能約略的評估各種可能性。

不過動物遺傳學家已經成功地發展出一些繁殖機制,去增進乳牛的牛奶產量、母雞的產蛋量、馬隻的速度和食用動物的生長速率……等。他們用的是曾經在狗身上也被證明有效的基礎遺傳原理。以下有一些對於多基因遺傳性狀的觀點,被認為符合這些原理:

*在謹慎的考慮之下,多基因遺傳性狀的表現是有一個範圍的,從最希望出現到最不希望出現的遺傳特徵都有可能被表現出來

舉個例子,現在有兩種交配情形:
1.兩隻種犬都具有理想的結構型態
2.有一隻種犬具有不理想的結構型態,或兩隻種犬的結構型態都不太理想
當我們比較這兩種交配情形所生下的後代時,可以預期第一種情形會有比較多數量的後代擁有理想的結構型態。不過因為是多基因性狀的關係,所以兩種交配情形所生下的仔犬,在結構特徵上都將呈現出一定範圍的差異。

*多基因性狀會受到“環境因子”的影響,進而最大化或最小化動物在遺傳上獲得的潛能

例如,一隻呼吸道感染的馬匹,將無法達到牠在遺傳上所獲得,在速度上的潛在能力。或是一隻在飲食上挨餓的乳牛,將無法產出牠在遺傳潛能上應該產出之最大量的牛乳
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文章泡泡拔 » 2006-08-26, 22:15

轉貼本文請註明出處:
犬髖關節狗友會(www.dogchd.net)泡泡拔 阮振維譯自www.offa.org


續上篇,接下來的觀念很複雜,大家可能要用心體會,有問題就提出來討論吧!

Heritability measures the phenotypic expression of multiple genes
as possibly modified by environmental influences and the degree to
which the resulting phenotype predicts the genotype.


The equation P(phenotype) = G (genetics) + E (environment) is a starting point.

This equation means the variation in phenotype presented comes about from
the complex interaction of the animal’s own inherited genotype with the
environment to which it has been exposed.

Using hip dysplasia (HD) as an example, some environmental factors include,
but are not limited to,overweight, rapid growth rate, early maturation, sex of
the animal, etc.

The most studied environmental influence on HD is caloric intake.
It is important to understand that heritability estimates do not refer
to the degree of inheritance, but rather to the degree that the additive
genetic component is reflected in the phenotype.


This is easier to understand using a trait for which most people have a greater intuitive grasp.
In dogs, wither height is a polygenic trait that may be modifi ed by the
environment. Height may be influenced by restricting calorie or vitamin
intake, certain environmental effects on hormones (such as early
spay/neuter), and other environmental factors.

Despite those potential environmental influences, height is recognized to be an inherited trait.
However, one cannot accurately predict the height of an offspring by
knowing the height of parents or siblings.
This is because polygenictraits have many complex genetic interactions, in addition to their
interactions with the environment.

Thus, when one is only able to measure the height of parents or siblings, one is measuring
their phenotypes, and not able to consider their genotypes and the various possible interactions of those genes.
It may be helpful to substitute “predictability” for “heritability” to further clarify this concept.

遺傳能力可以測量多個基因在表現型上的表達程度,而表現型究竟能真的被呈現出來多少,則可能被以下兩點所改變,一個是環境因子的影響,另一個是利用最終表現型所推測出來的基因型所以一切都要從這個公式開始:P(表現型)= G(遺傳因子) + E(環境因子)。這個公式的意義是,表現型在呈現上的差異,是來自於“動物本身遺傳到的基因型”“曾經暴露的環境”之間,所產生的複雜交互作用。

以髖關節發育不全為例,有一些環境因子包含在其中,像是體重過重、快速的生長速率、過早成熟與動物的性別……等,但不只侷限在這幾項。目前針對髖關節發育不全,被研究的最多的環境影響因素,是卡路里的攝取

有一個相當重要的觀念必須被釐清,那就是遺傳能力的評估,並不單純來自於基因上的繼承程度,更正確的說,應該歸因於綜合的遺傳元素反映在表現型上的程度。

上面這一段相當複雜,不過若是用一個大部分人都可以理解的性狀來作解釋,也許大家會比較容易瞭解作者想表達什麼:

在狗的遺傳中,身高 (前腳到肩膀的高度) 是一種可能受到環境影響而改變的多基因遺傳性狀。而可能影響身高的因素,包含了~限制卡路里或維他命的攝取、某些影響賀爾蒙分泌的環境因素(像是結紮),或其他環境因子。不過儘管潛在著許多環境影響因素,身高仍然被認為是一種遺傳性狀。

沒有人可以藉由瞭解雙親或兄弟姊妹的身高,而精準的預測出後代會有怎樣的身高。這是因為多基因遺傳性狀擁有許多複雜的遺傳交互作用,尤其是遺傳因子與環境因子之間的交互作用。因此我們能做的,只是去檢測雙親或兄弟姊妹,去檢測他們呈現出來的表現型,但是卻無法知道他們帶有的基因型,也無法知道這些基因之間可能存在的各種交互關係。

如果大家還是不清楚,或許把“遺傳能力(heritability)”這個詞換成“推測能力(predictability)”,可以幫助我們釐清以上的觀點。
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文章泡泡拔 » 2006-08-26, 22:21

轉貼本文請註明出處:
犬髖關節狗友會(www.dogchd.net)泡泡拔 阮振維譯自www.offa.org


~續上篇
Heritability estimates are usually determined through mid-parent offspring
analysis using statistical methods and express the reliability of the
phenotype as a guide to the predictive breeding value of the animal.

Heritability estimates are reported on a scale from 0 to 1.0 (0-100%).
These are expected to vary depending on the genetic background of the studied
breed population and will change over time through selective breeding.


If the heritability estimate for a given trait is 0.1, it is generally
considered low and the animal’s phenotype is not a good indicator of
the genotype (breeding value).


Genetic selection based on a single phenotype would yield poor results.


Although difficult to obtain for most hobby breeders, phenotypic information on
many offspring raised in different environments (progeny testing) would offer
additional insight into the parent’s genotype.


If it is between 0.2 and 0.3, the heritability estimate is generally considered
moderate. The animal’s phenotype predicts its genetic makeup
to a reasonable degree, and genetic selection based on the individual
animal’s phenotype is expected to yield slow yet substantial results.
However, more rapid results can be achieved if phenotypic information
on relatives (pedigree depth and breadth) is also considered. This also
increases the accuracy in predicting the animal’s breeding value and aids
in identifying carrier animals.

If the heritability estimate is between 0.4 and 1.0, it is generally
considered high and the animal’s phenotype is a good predictor of its
genetic makeup. In this case, rapid results can be obtained with genetic
selection based on phenotype.

遺傳能力評估

利用統計方法來對“雙親-後代”進行遺傳上的分析,可以得到一個稱之為“遺傳能力評估”的評估值。這個評估值代表了一個表現型的可信度,同時也是動物繁殖價值的指標(指能力上的價值而非金錢上的價值)。 “遺傳能力評估”值的級別是從 0 ~ 1.0 (0 ~ 100%)。

這些評估被認為有相當高的程度,必須依賴特定品種在研究上所獲得的遺傳背景。而隨著實行選擇性繁殖的時間增加,這些評估的值是會被改變的。

如果現在有一個遺傳性狀,它在“遺傳能力評估”上獲得的級別是0.1,那麼一般認為這是一個很低的分數,也代表這個表現型並不是一個好的指標,足以讓我們去推測基因型(或評估繁殖價值)。在這種條件下,利用單一表現型來作遺傳上的篩選,將會產生不理想的結果。

如果有大量的後代被飼養在不同的環境中,那麼從這些後代得到的表現型資訊,將可以幫助我們對雙親的基因型有更深入的了解,不過這對一般的業餘繁殖者是很難做到的。(泡泡爸:看來專業的繁殖者要具備的知識和能力是遠超過我們想像的。)

如果“遺傳能力評估”的等級介於 0.2 ~ 0.3 之間,那麼大致上這可以算是一個中等的分數。在這個分數下,我們可以利用動物的表現型,去合理的預測遺傳結構(基因型),也可以藉此進行遺傳篩選,也許進展會很快緩慢,但是卻是很踏實的。不過若同時考慮整個家族的表現型資訊(兼顧族譜的深度與廣度),那麼就可以在較快的時間內得到理想的結果,也可以讓我們更精確的去推測動物的繁殖價值,並有助於辨認帶原動物。

如果“遺傳能力評估”的等級介於 0.4 ~ 1 之間,基本上這被認為是很高的分數,代表這些動物的表現型是很好的推測指標,可以準確的預測基因結構。在這樣的狀況下利用表現型去作遺傳篩選的話,很快的就會獲得理想的結果。
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文章泡泡拔 » 2006-08-26, 22:37

轉貼本文請註明出處:
犬髖關節狗友會(www.dogchd.net)泡泡拔 阮振維譯自www.offa.org


Breeding based on individual phenotypes appears to be the
method used by most breeders, as available information on relatives
is somewhat limited. For traits considered to have moderate
heritability, this approach will reduce the frequency of an undesirable
trait in the progeny, but progress, while substantial, will
be slow.

Information on siblings of an individual animal, plus information on
the siblings of parents and grandparents, makes it possible for the breeder
to apply greater selection pressure against the disease. This results
in selection of animals with more ideal breeding values and provides a
more rapid reduction of the undesirable trait in the breeding program.

The following breeding selection criteria have been demonstrated
to more rapidly and effectively reduce the frequency of
undesirable traits:

1. Breed only normal dogs to normal dogs〞using hip dysplasia
as an example, Table 1 illustrates the outcome of matings based on
information extracted from the OFA database. A total of 444,451
progeny were identified where both parents had hip conformation
ratings. The percentage of dysplastic progeny increased as the sire*s
and dam*s phenotypic hip ratings decreased from excellent through
dysplastic. Reed (2000) reported equal genetic contribution on
progeny hip scores from the sire and dam.

2. Breed normal dogs that come from normal parents and
grandparents〞this employs the traditional horizontal pedigree
with emphasis on the most immediate three generations (50% genetic
contribution from each parent, 25% from each grandparent
and 12.5% from each great grandparent)

3. Breed normal dogs that have more than 75% normal siblings
〞this information is usually not available since most animals
in a litter become pets and are not screened for undesirable traits.
Breeders can add incentives to purchase contracts in an attempt
to gather this information, such as offering reimbursement for a
preliminary hip radiograph taken when the pet dog is spayed/neutered.



4. Select a dog that has a record of producing a higher than
breed average percentage of normal progeny〞if known, the
comparison of production performance between individuals is an
important criterion. For example, a stud dog with a track record
of producing 90% normal progeny is far superior to another dog
producing only 50% normal progeny.


5. Choose replacement animals that exceed the breed average
〞exert constant, consistent pressure to ensure overall breed
improvement.
In summary, achieving goals in breeding program depends upon the
ability to assess an animal*s predictive breeding value. Important information
to assist breeders in achieving their goals is available on the OFA
website through the database search option (www.offa.org).


利用動物個體的表現型來進行繁殖篩選,是目前大部分繁殖者所採用的方式,不過若想獲得整個家族的資訊,基本上還是有所限制的。如果是一個只具有中等遺傳能力的遺傳性狀,用這種篩選方法的確可以降低不想要的性狀在後代出現的頻率,雖然很有用,但是進展卻會很緩慢。---從個體的兄弟姊妹獲得的資訊,加上從雙親、祖父母的後代獲得的資訊,將可以幫助繁殖者用更好的篩選機制去對抗疾病。經過這樣篩選的動物將具有更好的繁殖價值,同時也可以快速的降低非期望性狀,在繁殖過程中出現的機會。

以下的繁殖篩選準則,已經被證明能夠更快速且有效的降低,非期望性狀出現的頻率:

1.只繁殖正常的犬隻,讓他們生出正常的後代—以髖關節發育不全為例,《表格一》是從OFA資料庫中擷取出來,可以用來說明各種交配情形會產生的後果。總共 444,451隻受檢驗的後代,他們的雙親都有髖關節結構的評分。當種公種母在髖關節的評分由極佳(excellent)降到發育不全(dysplastic),生出CHD後代的百分比也會隨之增加。在Reed於2000年發表的研究論文中,也報告了相同的結果。
Reed AL, et al: Effect of Dam and Sire Qualitative Hip Conformation Scores on Progeny Hip Conformation. JAVMA, 2000; 217: 675-680


2.繁殖雙親與祖父母都正常,而本身也正常的狗—這個準則利用了最接近的三個世代,所建立起來的垂直遺傳族譜(50%的遺傳貢獻來自於雙親,25%來自組父母,12.5%來自於曾祖父母)。

3. 只繁殖本身正常,且其兄弟姐妹有超過75%比率都是正常的犬隻—這個資訊通常不容易取得,因為大部分同胎的動物都會被賣作寵物,而且不會對非期望性狀做篩檢。所以繁殖者可以在飼主的購買合約中加入一些激勵條款,試圖去收集這些資訊。例如提供一些補助,讓寵物在做結?手術的同時,也能對髖關節作X光顯影的初步檢查。

4. 挑選一隻在紀錄上,生出正常後代的比率,比品種平均還要高的狗來做繁殖—如果在有辦法了解的狀況下,比較不同個體在繁殖後代上的表現,將是一個重要的繁殖準則。舉個例子,在選擇種狗時,一隻可以生下 90%正常後代的狗,是遠遠優於另一隻只能生下 50%正常後代的狗的。

5. 選擇超越品種平均的動物,來取代原本進行繁殖的動物—要施加持續而穩定的篩選壓力,以確保整個品種的進步。簡單的說,要達成在繁殖機制上的目標,必須倚賴我們在推測動物繁殖價值上的能力。利用OFA網站上的搜尋選項,可以幫助繁殖者獲得重要的資訊,進而達成他們的目標。
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文章泡泡拔 » 2006-08-26, 22:56

先跟大家說聲抱歉,遺傳學這個部份作者寫得滿深的,所以要把它翻得白話不是很容易,所以為了要讓大家看懂,我明天會針對一些詞做一些解釋,
希望能讓大家有收穫!

不過我想大家看完後,應該會發現一家犬舍該有的專業知識與能力,是遠遠超過我們想像的,臺灣的繁殖業的確還有很常的一段路要努力,否則所謂的
專業犬舍可能都只是一個空虛的口號!
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