Saturday, March 28, 2015

Discovering lethal recessive genes by Genomic testing

This is from the 2011 September Diary Route letter

In a technology version of the Ellery Queen detective story, AIPL scientists took the Genomic data set (covering Holsteins, Jerseys and Brown Swiss) and went looking for gene pairings that never show up in a living animal.    The assumption is that such a “haplotyte” (Genomic marker) must always be lethal in a homozygous pairing—either conception fails or embryonic death occurs.   Five were found:

Gene ID    Source ancestor        Year born     Frequency      Effect on

                                                                        Within breed     Conception       
Pawnee Farm Arlinda Chief
Willowholme Mark Anthony
Glendell Arlinda Chief,
Gray View Skyliner

Observer Chocolate Soldier
West Lawn Stretch Improver

Of interest is Willowholme Mark Anthony who is the lone Canadian and the newest line to be identified.  The majority of HH2 descendants come through a single daughter, Elysa Anthony Lea, who was dam of Comestar Laurie Sheik and thus progenitor to every “Comestar” sire used in Canadian or European AI.

Also of interest is Glendell Arlinda Chief, avoiding the HH1 carried by his sire Pawnee Farm Arlinda Chief but picking up from the “Burke” breeding on his dam’s side the HH3 shared by a premier Burke line sire of previous generations, Gray View Skyliner.

The difference between these haplotytes and earlier lethal gene recessives

Many lethal recessives are expressed by a visually defective or stillborn calf.    A recent exception was DUMPS in Holsteins, which produced early term abortions (similar to the above Haplotytes).    Here is a list of lethal recessives for which AI sires are tested and noted when carriers:
Holstein     Brachyspina (BY), Cervical Vertebral Malformation (CV), Bovine Leucocyte Adhesion Deficiency (BL), Mulefoot (MF), Pinktooth (PT), Bulldog, Hairless, Prolonged Gestation.
Jersey         Rectal Vaginal Constriction (RVC), Limber Leg (LL).
Brown Swiss  “Weaver” (W), Spinal Muscular Atrophy (SMA).

But there are other recessive effects, for example in Ayrshire (thus also Swedish Red) you have the “fishy milk” gene—a recessive that gives the milk an oily consistency and an off flavor.   

Red hair color in Holsteins, White spots in Jerseys—these are “benign” recessive genes.    Horns are in fact a recessive that everyone experiences (the Polled gene is the single-allele “dominant” vs. horns).

Can we truly avoid all lethal recessives?

Yes, we can—if we want to do so.     In earlier eras, we did it by never sampling “carrier” sons of the higher ranking carrier parents.     Thus when “Wayne” had Mulefoot, only his MF “free” descendants (like the dam of ToMar Blackstar) were considered for AI.      Likewise if a sire line had been widely dispersed, as was true with “Bell” (and thus BLAD), most dairymen just decided they had enough of that line, and the market for sons/grandsons dried up.     

However, if you are the Jersey breed and have 23.4% (nearly a quarter) of your genes tied up in that single “Chocolate Soldier” sire line (which means Top Brass— Brook—Montana—Jace) (which means Soldier Boy—Sooner—Berretta and Hallmark—Paramount) (which means the dams behind Duncan—Lester—Lemvig and QS Royal—Alf and Judds Admiral) the temptation will be great to just ignore this and drive on, even if it means putting the breed’s high fertility reputation somewhat in jeopardy.

Fertility is the basis of all Productivity

The beginnings of the AI industry were not a competition over who had the best genetics—it was a test of whether the AI conception rate would be superior to natural service fertility.     Most dairymen in that era had multiple animal species, and understood that “reproduction” came first before any “production” that followed it—no calf, no milk thus no milk check.     Our industry has played with substitutes for a regular reproductive rate, like rBST, and covers up lower reproductive rates with OvSynch and sexed semen, but the increased demand for cows with “longevity” and ‘strength” are an indication that more dairymen still recognize sound fertility as a primary selection criteria both in genetics and herdsmanship.

Single trait genetic selection began to chip away at fertility quality

ABS (in its pre-Grace days) advertised “every sire proved great” and from its base of the largest network of inseminators nationwide, began promoting “genetics” as the basis for AI utility.    They believed, and were supported by most extension dairymen, that “milk” was the first (if not the only) trait worth buying and belittled the “type” and “cow family” emphasis of organizations like Curtiss and Carnation.

Unknown to anyone however, was the internal insemination data reports, indicating a steady 1% decline in conception rate each year.    ABS sires were selected on “milk” first, and even though their veterinary staff routinely culled sires at the bottom of their ERCR reports, the overall average kept declining. Why?
No one knew, because USDA only summarized 305 day ME lactations, with no adjustments for calving interval, and Breed Associations only summarized type scores.    The data was there to link fertility to genetic selection, but no one bothered to look at it until it started to impact on AI semen sales.

Composite indexes to “rank” sires remain a “single trait selection” method

The purebred sector fought the scientific sector for decades in promoting a multiple-trait approach to the breeding of superior cattle, with more of an emphasis on lifetime performance.    To draw the purebred sector under the technocrats’ wings, the concept of multi trait indexing (weighting production and type traits by a formula into a single TPI or $NM value) was borrowed from the terminal cross poultry and swine species and sold to us as applicable to dairy sire and cow selection.
At the beginnings of this effort, lots of data was collated to “prove” that the higher indexing sires would outperform average indexing sires by a ton of milk per lactation.    Over time, once the indexing concept had taken over, the need for comparisons died away… but on the last genetic base change, it was noted that “proven” sires now only had a $125 Lifetime “Net Merit” advantage over jumper sires.

Why all indexes fail over time

Today we have Genomic testing as the latest fad in “indexing”—an attempt to save a generation of selection by skipping the sire sampling process and calculate sire rank from DNA haplotytes.    This method has been tried twice in New Zealand (and has failed twice to identify the “top” sires even as it succeeds as here in screening out the least likely prospects).     Expectations remain unreasonably high.

The obvious inference not being made is this:  genes can be identified as causal to individual traits, as that is a biological function of gene transmission; however there is no “genetic” link to any economic factors external to the biology of the cow on which all “ranking” indexes are based.

Put simply, we can rank animal performance in a current generation by any “index” reflecting current economic conditions; but we cannot predict future economic viability from any prior generation’s rank given the only genetic basis for improvement is in the synergy of biological traits in selection.

The single trait selection nature of indexing promotes a suppression of heterosis vigor

Here is a simple factoid:   Only four of the current “top twenty” progeny tested AI sires were part of the “top twenty” Genomic tested sires in the first year of G sire release to AI service.    Of the realized “top twenty” [Holstein] sires, the lowest initial rank under G estimation was 844 (out of 1015 G sires).

This should surprise no one.    The top five sires for PD Milk at AI levels of Rel% in the 1966 USDA sire summary are virtually unknown today—none of them produced a sire line that lasted more than three generations.    Today’s exceptional sires become the definition of “average” in three generations and in the past we would be seeking a new sire line by then.  

Because of this, we must recognize that “heterosis vigor” requires a periodic change in genes selected to produce the level of heterozygotic response in correlated groups of genes that impact on realizable milk type and health trait performance, with fertility the main prerequisite within health selection.

The formula for Productive Life estimation is a useful example

Buried within all the traits used in estimating PL values on sires too young to have “matured” daughters is an assumption that smaller cows last longer than big cows.   This is exactly the sort of trait weighting that becomes nonproductive over multiple generations, as lost size leads to lost productive capacity.

The underlying statistics indicate the shortest herdlife is experienced on the smaller “frail” cows.   The bias against “large” cows is more based in the general prejudice against “show cows” who tend to be in the highest score ranges for stature, exceeding the dimensions of typical freestall housing.     But those cows who reach maturity and excel in lifetime productivity will be larger than average in weight (size) and average to slightly above in stature (upstandingness).      Lots of data supports this.

A good example of how assumptions can trump reality is the famous Regancrest Elton Durham CV.
His progeny data set has been as high as +4.0 for PL on matured daughters, but his tendency to sire a “large” cow regressed his PTA- PL values to +2.0 before Genomics, and he is now –0.2 PTA- PL as a result of being tested for Genomics (and possessing all the haplotytes for “size” than are currently under official discrimination).    This negative assumption is weighted into descendants like “Barbie”.

“Narrow” young cows are the surest route to “frail” cows that never get old enough.   Keep that in mind.

Inbreeding is not pedigree based—it is index based

Think the Kiwi BW is better than the German RZG or the US $Net Merit is better than the Canadian LPI?    Think again.    None of them produce more than three generations of improvement without the support of a 40% cull rate to sustain their data.

Three generations exchanges 87.5% of the initial gene possession.    At that point it is worth while to consider how many limiting homozygous gene pairings were created.

Rotating sire generational focus avoids the true inbreeding effect, allowing in new sires that can produce a “hybrid vigor” effect—a shift from milk yield to component %s, a shift from angularity to substance in physiques, a shift in favor of healthier fertility, as reflected in sires you choose to use.

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