7 Congenital Defects

We are now proposing genetic testing for seven congenital defects that are either lethal or responsible of important economic losses in Belgian Blue Cattle Breed. We have identified the causative mutation for five of them and can therefore propose a direct test with 100% sensitivity and specificity (no false negative, no false positive). For two of them, we only know the piece of chromosome where the mutation is located, for these, we are proposing indirect tests, they are slightly less sensitive (an animal can be falsely declared non carrier, in less than 5% of the tests) and also less specific (an animal can be falsely declared carrier, in less than 5% of the tests).

The seven congenital defects are the following:

1 - CMDI: Congenital muscular dystonia I

• Lethal within days around birth
• Default in muscular relaxation
• Mutation identified, direct test proposed

2 - CMDII: Congenital muscular dystonia II

• Lethal within hours around birth
• Default in neuro-muscular relaxation
• Mutation identified, direct test proposed

3 - CTS: Crooked Tail Syndrome

• Not lethal per se but > 25% euthanized on welfare grounds
• Growth retardation, stocky head, extreme muscular development, scoliosis, spastic paresia: economic losses
• Two mutations identified in the same gene: combined direct test proposed to detect both mutations

4 - DW: Severe growth retardation (dwarfism) and decreased resistance to infections

• Not lethal per se but 40% died before 1 year from recurrent infections
• The remaining 60% are severely growth retarded and culled for health related reasons: economic losses
• Mutation identified, direct test proposed

5 - HAM: Gingival hamartoma and osteopetrosis

• Lethal around birth, some can survive a few weeks
• Complications during parturition, cows often culled
• Vascular mass (1 to 15 cm) in the mouth, abnormal skull shape
• Blindness
• No bone marrow cavity in the long bones (osteopetrosis)
• Mutation identified, direct test proposed

6 - PG: Prolonged Gestation

• Parturition fails to occur, upon medical induction, calves are born alive but die within hours
• Gestation can last up to 14 months
• Mutation localised, indirect test proposed

7 - AP: Arthrogryposis and cleft Palate

• Lethal before birth
• Arthrogrypose, cleft palate, blindness, umbilical hernia
• Complications during parturition, cows often culled
• Mutation localised, indirect test proposed

SUMMARY

Type of test, test proposed since year x , carrier frequency in the Belgian Blue population when the test was initially proposed.

Direct tests
Congenital muscular dystonia type I	2006	~15%	(CMDI)
Congenital muscular dystonia type II	2007	~6%	(CMDII)
Crooked tail syndrom (mutation 1)	2008	~25%	(CTS)
Dwarfism	2009	~28%	(DW)
Hamartomas	2010	~10	(HAM)
Crooked tail syndrom (mutation 2)	2010	<1%	(CTS)

 

Indirect tests (Marker Assisted Selection)
Prolonged gestations	2010	~15%	(PG)
Arthrogryposis syndrome	2010	<2%	(AP)

Pictures illustrating the seven defects:

NEW MODALITIES FOR GENETIC TESTING IN BELGIAN BLUE CATTLE BREED (SEPTEMBER 1ST 2011)

We are now proposing genetic testing for seven congenital defects that are either lethal or responsible of important economic losses. We have identified the causative mutation for five of them and can therefore propose a direct test (CMDI, CMDII, CTS, DW, HAM). We two of them, we only know the piece of chromosome where the mutation is located, for these, we are proposing indirect tests (PG, AP).

Here are the four possibilities for genetic testing, with their respective price (VAT included)

CHOICE 1 :

DNA extraction (from blood or sperm) and one direct test (CMDI, CMDII, CTS, DW, HAM) :
Cost : 70 euros

Possibility to mention on the order form that, if this first direct test is negative (non carrier animal), receive the results for all five direct tests for a total of 130 Euros.

CHOICE 2 :

DNA extraction (from blood or sperm) and all five direct tests (CMDI, CMDII, CTS, DW, HAM) :
Cost : 130 euros

CHOICE 3 :

DNA extraction (from blood or sperm) and all the indirect tests (PG, AP) :
Cost : 130 euros

CHOICE 4 :

DNA extraction (from blood or sperm) and all the tests (CMDI, CMDII, CTS, DW, HAM, PG, AP) :
Cost : 220 euros

REMARKS:

We can’t offer price reduction for females or for more than 16 samples anymore. If we already have DNA from your animal in our database (before September 1st 2011) and if you ask for additional testing, the same procedure will be followed, but with a reduction of 30 Euros for DNA extraction.

GENETIC TESTING, PRINCIPLES AND APPLICATIONS

These seven congenital defects are characterized by a recessive mode of inheritance: animals can have two copies of the normal (+) allele (+/+), two copies of the defective (D) allele (D/D), or one of each (+/D). D/D animals present the disease, while +/+ and +/D animals are generally healthy. +/D animals, however, are said to be “carriers” and will transmit the D allele to halve their offspring. The mating between two carrier animals will produce one fourth of affected D/D offspring (Figure 1).

Figure 1: Mode of inheritance of a recessive defect

If one could identify +/D animals despite the fact that they don’t exhibit the symptoms of the disease, it would be possible to eliminate them from breeding programs or at least avoid matings between carriers. This would allow immediate eradication of the genetic defect from the population and avoid the economic losses associated with it.

It has recently become possible to identify the genes underlying genetic defects and the mutations in them which cause an allele to be D(efective). It has also recently become possible to use molecular biology techniques to rapidly analyse a DNA sample from an individual and to determine whether it contains a D allele, i.e. it is now possible to directly detect carriers if the gene and causal mutation underlying the defect are known. If only the localisation of the mutation is known, indirect tests (marker assisted selection) can be proposed.