Установлено точное наследование риджа Опции

[Nana]

We have just learned that the specific genetic mutation responsible for the ridge in the Rhodesian Ridgeback has been found.

The work was done by Dr. Leif Andersson at Uppsala University in Sweden in collaboration with researchers at the Broad Institute/MIT here in the U.S. and the Swedish University of Agricultural Sciences. A paper will be published in the coming months, and Dr. Andersson expects a genetic marker test to be available in the fall, pending licensure, etc.

That is all the information Dr. Andersson has given us, along with his permission to disclose it to the Ridgeback community. We know you are as thrilled as we are.

As many of you know, Dr. Mark Neff, in collaboration with RRCUS, was also searching in parallel for the same marker. While Dr. Neff's efforts were not responsible for this discovery, we all agree it is wonderful for the breed.

We are sure this will be a subject of intense interest at Dr. Bell's seminar next Wednesday at the National Specialty in Ohio, as he will be discussing the implications of a direct-marker test for breeders.
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Коротко:
Сотрудничество шведов и американцев привело к тому, что 23 мая на семинаре в Америке на Национальной выставке в Охайо будет объявлено о точном наследовании риджа и маркеровочных тестах. способных определить носителей. И т.д.

[Nana]

Permission is given for this to be crossposted.
Дано разрешение на перепечатку.

Uppsala September 24, 2008
Университет Uppsala, Швеция

A statement concerning the genetic basis for the hair ridge and the congenital malformation dermoid sinus in Rhodesian Ridgeback dogs
Заявление, касающееся генетики риджа и дермоидного синуса.

1. The inheritance of the Ridge
Наследование Риджа.

All our data and all data we are aware of indicate that the ridge is inherited as a fully dominant trait. The dominant allele causing the
ridge is denoted R whereas the recessive wild type-allele is denoted r. This means that a ridged dog may either be homozygous (R/R) or heterozygous (R/r) for the Ridge allele whereas all ridgeless dogs should be homozygous r/r for the normal allele. The result presented in our Nature Genetics paper from 2007 (Hillbertz et al. Nature Genetics 39:1318-1320) provided conclusive evidence that the mutation causing the ridge in Rhodesian Ridgeback as well as in Thai Ridgeback dogs is a 133 kb duplication on dog chromosome 18. [A duplication means that each Ridge chromosome has two copies of this 133 kb fragment whereas a normal chromosome has only a single copy. It is this doubling or duplication of the chromosome region that constitutes the Ridge mutation.] So far all tested dogs with the characteristic dorsal hair ridge have been heterozygous or homozygous for this mutation whereas all ridgeless dogs we have tested lacked the duplication. The duplication contains four complete genes (FGF3, FGF4, FGF19 and ORAOV1) and we assume that it is the higher than normal expression of one or more of these genes, attributable to their greater number, that leads to the development of the hair ridge.
По имеющимся данным ридж наследуется простым доминантным способом - собаки с риджем на спине могут иметь как два доминантных аллельных гена (RR), так и быть гетерозиготными по данному признаку (Rr). Собаки без риджа имеют два аллельных рецессивных гена (rr). В 2007 г. ученые установили, что мутация, ответственная за проявление риджа в области спины (как у РР, так и у ТРД) - это дубль-участок 18-ой хромосомы Дубль означает, что участок хромосомы, ответственный за ридж, имеет не один фрагмент, как у нормальных - безриджевых собак, а два). Все собаки с риджами на спине имели этот дубль , а собаки без риджа - нет. Этот дубль-участок содержит четыре группы генов(FGF3, FGF4, FGF19 and ORAOV1).

2. The genetic basis for dermoid sinus (DS)
Генетическая основа Дермоидного синуса.

DS does not have such a simple inheritance as the Ridge but our data clearly showed that the Ridge mutation (i.e. the duplication described above) is the major risk factor for the DS malformation in Rhodesian Ridgeback dogs. Most DS dogs in our study were homozygous R/R (10 of 12) for the Ridge mutation but two were classified as heterozygous R/r. However, DS or DS-like malformations also occur in humans so it
is possible that this type of=20 malformation may occur in dogs in the absence of the Ridge mutation. But its frequency in unridged Ridgebacks should be as rare as it is in non-ridged breeds.
ДС не имеет простого наследования. Но данные ясно показывают, что мутация, вызывающая проявление риджа на спине (описанный выше дубль-участок), является основным фактором риска в формировании дермоидного синуса у риджбеков. Большинство собак с наличием дермосинуса, изученных нами, были гомозиготными по признаку риджа (RR) - 10 из 12. Две собаки были гетерозиготными (Rr). Однако ДС или схожие с ним образования имеются и у человека, и у собак без риджа. Но частота проявления ДС у риджбеков без риджа должна быть ниже, как и в безриджевых породах.

3. DNA tests
ДНК тест.

In our Nature Genetics paper we described a simple DNA test that can be used to identify the presence of the Ridge mutation (the duplication). Any DNA laboratory skilled in the art of DNA testing can perform this test and there is no patent protecting its use. It is therefore easy to distinguish a ridged dog (R/R or R/r) from a ridgeless dog (r/r) by the DNA test but we have not yet established a diagnostic test that on a routine basis can distinguish animals that are heterozygous carriers (R/r) from homozygous ridged (R/R) with 100% certainty. The establishment of this test will require some further research.
В журнале Генетика был описан простой тест на определение генотипа риджа. Любая ДНК лаборатория может выполнять такое тестирование. Но в то время как тест точно определяет риджевых собак как гомо, так гетерозиготных (RR или Rr) от безриджевых (rr), но все ещё ошибается в тестировании гомозигот от гетерозигот. Поэтому для изготовления этого теста потребуются дальнейшие исследования.

4. Recommendations for breeding
Рекомендации по разведению.
Самый простой способ снизить частоту проявления ДС в породе - это снизить поголовье гомозиготных (RR) собак. Это можно сделать введением безриджевых особей в разведение. Бридинг между RR и rr даст всех щенков с риджами и все будут гетерозиготами Rr. И таким образом, сохраняя эту характеристику (ридж) в породе можно снизить уровень ДС. И т.д..... ..... если же бридеры захотят полностью убрать проблему ДС из породы, то надо избавляться от мутации под названием ридж.. И т.д.

The most straightforward way of reducing the incidence of DS in Rhodesian Ridgeback dogs is to reduce the frequency of homozygotes for the Ridge mutation. This can be accomplished by allowing the use of ridgeless dogs for breeding. While we are aware that dogs with a DS are not usually kept for breeding, matings between homozygous (R/R) ridged dogs (presumably without DS) and ridgeless dogs (r/r) would give progeny all of which would be heterozygous ridged (R/r) and therefore show ridging, and the incidence of DS would be low. In matings between a heterozygous ridged dog (R/r) and a ridgeless dog (r/r), 50% are expected to be heterozygous ridged (R/r) and 50% are expected to be rid geless (r/r). In these matings no homozygous ridged progeny, which are the major problem as regards the incidence of dermoid sinus, would occur. It should therefore be possible to retain the ridge while keeping the incidence of DS to its absolute minimum. It would be useful to develop a diagnostic test to distinguish carriers (R/r) from homozygotes (R/R) because this would allow breeders to avoid matings such as R/R x R/r that will produce homozygous ridged (R/R) progeny.
It will of course be up to the individual breeders and to Ridgeback breeding organizations to decide whether they prefer to keep the Ridge and minimize the incidence of DS using the approach described above or whether they would like to completely eliminate the problem with DS by allowing the Ridge mutation to disappear from the population over time. If one decides to eliminate the Ridge mutation it should not be done too quickly (during a few generations) since that will lead to increased inbreeding in the breed as too many potential breeding animals are eliminated.

Acknowledgement: We would like to thank Bruce Cattanach for valuable
discussions on this subject.

Leif Andersson1, Kerstin Lindblad-Toh1,2 and Göran Andersson3

1Department of Medical Biochemistry and Microbiology, Uppsala
University, Box 597, SE-751 24 Uppsala, Sweden.

2Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge,
Massachusetts 02142, USA.

3Department of Animal Breeding and Genetics, Swedish University of
Agricultural Sciences (SLU), Biomedical centre, Box 597, SE-751
24
Uppsala, Sweden.

Сообщение отредактировал Nana - 27.9.2008, 2:22