Clinical Genetics Flashcards
what is a gene loci?
defined position of a gene on the chromasone
what are autosomal chromosomes?
any chromosomes that are not X or Y
what are genes close together on the chromosome known as?
linked
what are sex linked chromosomes?
those on the sex chromosomes
what are alleles?
alternative forms of genes which have the same locus
what are the types of alleles?
dominant
recessive
co-dominant
what is epistasis?
non-allelic gene interaction
what is incomplete penetrance of a gene?
gene is blocked by another
what is variable expressivity?
genes being modified by other genes leading to a range of signs and symptoms in individuals
what mutation is responsible for short tales in Manx cats?
dominant M mutation
normal cats are mm
what is an example of a gene with variable penetrance?
M gene in manx cats - while it is dominant sometimes not the whole tail is missing
what happens to Manx cats with MM?
die in utero as it is a lethal gene
what is an example of epistatic gene interaction?
coat colour in labradors
what does the 3 labrador coat colours result from?
differences in 2 gene loci that affect pigment expression
how is labrador coat colour determined?
presence of eumelanin in fur (and therefore dark coat) is dominant -E
yellow lab only possible with ee
concentration of pigment is determined by a different gene (B, b)
black (B) is dominant - bb required for brown
what would an eebb larbrador look like?
yellow lab
brown nose, fur and lips
how is tortoise shell coat produced in cats?
epistatic effects of the sex linked orange (O) gene on the autosomal black and tabby genes
Torty cats are heterozygous for the O gene. In every cell only one copy of the X gene is active, and it is random which copy is active. (will be O + or O-)
For cells where the O gene is active the hair coat will be orange, for cells where it is inactive the hair coat will be black or tabby, depending on the cats autosomal genetic makeup for the black tabby genes.
in what type of dog is the MDR1 dominant mutation seen?
herding dogs
what is the result of the MDR1 gene mutation?
these dogs are more susceptible to drug toxicosis due to an alteration in the protein responsible for clearing drugs over the blood brain barrier and excreting them
what protein is affected by the MDR1 gene mutation?
P- glycoprotein
what are 3 commonly used drugs who’s clearance is affected by the MDR1 gene?
ivermectin
milbemycin
selamectin
what can be done if an MDR1 risk dog is in practice?
genetic testing
use of drugs that are not known to cause problems
what genetic mutation is found in some greyhounds?
cytochrome P450 is altered so they have reduced ability to clear anaesthetic drugs from the brain and so recover slower
is genetic testing available to see if there is cytochrome P450 mutation yet?
no
what do dog blood types represent?
genetically determined markers on the surface of the animals RBC
what is antigenicity?
Antigenicity - the likelihood that the immune system will react and make antibodies (alloantibodies) against a foreign substance.
what is the blood grouping system formed of?
allelic blood types (two or more markers on same gene locus)
what blood type do around 70% of dogs have?
DEA 1+
when can DEA sensitisation occur?
if DEA 1 - dog is exposed to DEA 1 + blood they will form alloantibodies to the antigens on the DEA + blood
this can lead to delayed transfusion reaction (haemolysis) or severe transfusion reaction if another DEA 1+ transfusion is performed
when is cross matching of donor and recipient blood needed in dogs?
transfusion history unknown
previous transfusion
previous transfusion reaction
what blood type must be given to dogs if testing is not possible and blood type is unknown?
DEA 1 -
what are the 3 blood types found in cats?
A
B
rare AB
how does AB cta blood type interact with A and B?
AB recessive to A and co-dominant to B
how dies cat type A blood interact with the other blood types?
A is dominant (to be type B cats must be homozygous BB)
what is the most common blood type in cats?
A - 95%
why must all cat blood donors and recipients be cross matched?
cats possess naturally occurring antibodies to other blood types that they don’t have
which blood type in cats produces higher titre of opposing antibodies?
type B has higher titre of anti-A antibodies
what cat breeds are more likely to have blood type B?
Birmans, British shorthair, Devon rex Cornish rex, Ragdoll, Turkish Angora, Turkish Van
what cat breeds are more likely to have blood type A?
DSH, Siamese, Main coon, American shorthair, Bengal, Norwegian Forest
what is neonatal isoerythrolysis?
kittens receive anti-A antibodies to their own blood type (A) in mothers colostrum (as she is B and so has anti A) which leads to haemolytic anaemia and possibly death due to immunce destruction of their RBC
what parent blood type combination can lead to neonatal isoerythrolysis in kittens?
Type B queen and type A/AB tom
type A is dominant
what can be done to prevent neonatal erythrolysis in kittens?
blood type breeding pair to ensure that compatible blood types only mate (e.g. A and A, AB and A, A and B(Tom)) or B and B)
take kittens off cat for first 24-26 hours (ethics)
what are kennel club screening programmes used to do?
identify the likelihood of a heritable disease being passed on by parents and advise owners on the advisability of breeding
what are the 2 main ways to test for heritable diseases?
genetic test - for directly inherited diseases
screening tests - for more complex, slower developing issues
how is hip scoring performed?
VD radiograph of pelvis hips and femurs
strict guidelines for positioning and identification
how is a hip score supplied?
2 experts analyse images and score them
what is the total hip score out of?
53 for each hip
106 in total
what is a better hip score?
lower is better
what is the issue with hip scoring?
dogs with poor hips will likely not have x-rays submitted for grading
what is the elbow scheme designed to assess?
elbow dysplasia
what radiographic view is needed for elbow scoring?
medio-lateral
how is elbow dysplasia scored?
grade 1-3
if elbow scores are different the higher of the 2 is used
what is involved in the Kennel Club eye scheme?
panel of ophthalmologists assess for 12 hereditary eye conditions
how often is the eye scheme assessment renewed?
dogs should be seen every year while breeding
when is the first eye exam for the eye scheme performed?
6-12 weeks
when do dogs no longer need to be assessed under the eye scheme?
post breeding ~8 years old
what eye conditions are screened for under the eye scheme?
glaucoma, lens luxation etc
evolving list as more conditions/breeds added to watch list
what is Chiari malformation?
fault in the development of the skull, causing part of the brain to protrude from the opening at the back of the skull
what is Syringomyelia?
the presence of one or more fluid-filled pockets that may develop in the spinal cord, called syrinxes
how can dogs be assessed for Chiari - like malformation and Syringomyelia?
MRI scans of at risk breeds
what breeds are at risk of CM/SM?
cavalier king charles spaniels
griffon bruxellois
at what age should screening for CM/SM start?
> 1 year old
what breeds are assessed by the respiratory function grading system?
french bulldogs
pugs
english bull dogs
how is the respiratory function grading performed?
chest is auscultated by trained vet before and after 3 mins of quick paced exercise
what are the respiratory function grades?
0 (clinically unaffected) -3 (severe)
what is the aim of the heart screening scheme?
reduces chance of breeding puppies with MVD
what dogs are involved in the heart screening scheme?
cavalier king charles spaniel
what is assessed on heart screening?
murmur grade
mitral valve prolapse
how are cavalier king charles spaniels scored on the heart scheme?
assigned a risk of getting mitral valve disease and risk of passing this condition on to offspring
uses a traffic light system
what are the grades used for murmur and mitral valve prolapse during heart scoring?
murmur grade 0, 1, 2 or 3+
mitral valve prolapse - 0, 1, 2 or 3
what does the location of the grades on the traffic light system of the heart scheme depend on?
age at testing
what is cat genetic screening used for?
planning breeding programmes
what can only be detected in cats through genetic testing?
late onset diseases or carrier status (recessive allele)
how are cat genetic samples obtained?
mouth swabs - ensuring cheek cells are collected no just saliva
what can be screened for during cat genetic testing?
diseases
coat colour
blood types
when choosing what diseases to genetically screen cats for what must be considered?
breed predisposition - no need to screen if it is breed specific
