Keeshond Club Genetic Counselling Scheme

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Keeshond Club Genetic Counselling Scheme

• December 4, 2009
• Stephen J.G. Hall
• University of Lincoln

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Background

• The idea of a genetic tendency to epilepsy was
  first published in 1964. EEG investigations
  (1970s) proved fruitless.
• In late 1980s the late Dr. Margaret Wallace
  carried out pedigree analysis of 15 animals
  diagnosed by vets as epileptic and of 34 litters
  that didnt show the condition.
• The simplest hypothesis a single non-sex-linked
  recessive gene was tested by assuming both
  parents of an affected pup were carriers.
• For 26 litters of which both parents were thought
  to be carriers, numbers of normal and affected
  progeny were known (91 and 29 respectively). This
  is the same, statistically, as a 31 ratio which
  is what would be expected from the hypothesis
  proposed. All the fitters were found to be inbred
  to either a dog born in 1971, or to his great
  grandsire.

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Operation of the scheme

• In 1989 following a lecture by Dr. Wallace the
  Keeshond Club decided to start a genetic
  counselling scheme and when Dr. Wallace retired,
  I continued with it.
• Veterinary practice and genetic counselling have
  been completely separate I play no part in
  diagnosis and will only enter an animal on the
  list of carriers if it is a parent of an
  epileptic and if this is communicated to me by
  the Clubs scheme co-ordinator.

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Uptake of the scheme

• Breeders who anticipate using specific animals
  for breeding, provide pedigree details to the
  co-ordinator who forwards them to SJGH.
• Numbers of these notifications, and of requests
  for advice, fluctuate from year to year (next
  slide, where trend lines are also given).

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Numbers of advices requested and of animals
notified to the scheme
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Criteria for approval of matings

• Advice on matings is based purely on a
  calculation of the probability that a resulting
  pup will be a carrier. Other factors, such as
  inbreeding, are not taken into account.
• A threshold was set at the start of the scheme a
  calculated probability of greater than 0.26 (26)
  would disqualify the mating.
• The rationale behind this threshold was explained
  in a scientific publication (Hall Wallace,
  1996).
• Generally, a high proportion of matings are
  approved (next slide, with trend line).

Vet. Rec. (1996) 138, 358
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Percentages of proposed matings that were approved
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Trends in calculated carrier probabilities

• The next slide shows a possible downward trend in
  the carrier probabilities of proposed matings.
• However, this is not strong evidence of a
  reduction in the frequency of the recessive gene.
• Perhaps breeders are making their own
  calculations or estimates and are no longer
  submitting matings for advice that are likely to
  be very near the threshold.

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Average carrier probabilities of proposed matings
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Is the scheme working (1)?

• In addition to the trend implied in the previous
  slide, there is a downward tendency in the
  carrier probabilities of animals being notified
  to the scheme
• This would suggest the frequency of the recessive
  gene is declining, at least in the segment of the
  breed that uses the scheme

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Average carrier probabilities of all animals
notified to scheme
Year of birth of dog
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Is the scheme working (2)?

• There is more powerful evidence for a beneficial
  effect. This was found in a project funded by the
  Canine Supporters Charity.
• KC records were examined in 2004. It was found
  that many of the matings had not been referred to
  the scheme.
• Carrier probabilities were calculated for all
  registered litters.
• Evidently (next slide), over the breed as a whole
  carrier probability is declining, i.e. the
  frequency of the recessive gene is declining.

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Average carrier probabilities of all KC
registered Keeshond litters
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Next steps

• Ideally, there would be a direct DNA test by
  which carrier animals would be identified.
• However, this would require a sample of at least
  12 epileptic animals and also of non-epileptics.
• Repeated efforts have been made to contact the
  worker at Cambridge University reported to be
  particularly interested in a direct DNA test,
  with a view to coordinating the scheme with
  proposed research work, but these attempts have
  been rebuffed.
• However, if a DNA test does appear, it will be
  much easier to put it into effect if the
  frequency of the recessive gene has already been
  reduced. Accordingly, it is suggested that the
  current scheme continues to offer real benefits
  to the breed and should continue to be supported.
• SJGH 4 December 2009