The story of DNA and the dairy industry – so far

In 1953 a group of international scientists, which included, Nobel prize winning New Zealander Maurice Wilkins, discovered the DNA double helix.

Remarkable as it was, they could not have predicted the impact this would have on the field of science.

It was quite literally, a step into the great wide open – propelling the world into unheralded potential for human and animal science.

What is DNA?

DNA - Deoxyribo Nuclic Acid
Each human has 50,000,000,000,000 cells and 25,000 to 35,000 genes.

Inside most cells is a nucleus which contains 99.9% of a person’s genes, there are also Mitochondria (which take in nutrients, break them down, and create energy for the cell) which contain a few genes.

DNA is a double stranded molecule composed of sugar, phosphate and four different basis: Adenine, thymine cytosine and guanine - these make up the genetic code – the number and order of the four basis decide what you are, for example, a human, a chimpanzee, or a cow.

DNA fact

If you were to line up all the DNA containing all of a human’s genes it would measure 1.5 metres long – but it is coiled so tightly that it fits into one cell nucleus.

Chromosomes

The long molecules of DNA containing genes are organised into pieces called chromosomes. Humans usually have 46 chromosomes or 23 pairs, cows have 30 pairs.

When was the structure of DNA discovered?

In 1953, a group of international scientists discovered the DNA double Helix. The scientists were: Maurice Wilkins, Francis Crick, Rosalind Franklin, Linus Pauling, and James Watson.

The discovery of the double helix identifying the structure of DNA was the key to unlocking all the potential genetic information contained within the genome providing the catalyst for progressing both human and animal science.

When did LIC begin its research into DNA?

For decades before the discovery of the double helix structure, it was known that genetic material or traits were passed from parents to progeny, but not how.

Dairy farmers and LIC had been making breeding decisions based on physical appearance (conformation) and milk production measured through herd testing for 10 to 15 years before the discovery of the DNA structure, selecting animals genetically superior in different and desirable traits.

But DNA is the ‘black box’ that contains the vast majority of important information.

In the early 1990s LIC’s research started began laying a pathway to understanding and identifying genes for specific traits that had an important economic impact on dairy cows.

LIC began investigating the possibilities of using DNA information to add value to the New Zealand dairy herd in 1993.

What are traits?

Each cell in the human body contains about 25,000 to 35,000 genes, which carry information that determines your traits. Traits are characteristics you inherit from your parents; this means your parents pass some of their characteristics on to you through genes.

How did LIC first utilise this new science?
In the early 1990s LIC was successful in identifying two genes – the first discovered for dairy cattle - possibly the first in livestock.

LIC utilised this information immediately, for pre-screening and selecting bulls entering the Sire Proving Scheme (SPS) on the basis of both genes and BW (breeding worth) to ensure the best sons were selected for SPS.

For a number of years LIC continued on that path of research trying to identify more genes and struggled to find more significant effects.

Then, at about the time it found a number of promising indicators of possible genes and was about to start intensive work in this area, a new technology came along and changed the landscape.

Sequencing the genome – changed LIC’s research strategy.

Understanding and knowledge about DNA has changed significantly over the past ten years due to the ability to sequence the genome.

What is DNA sequencing?

DNA sequencing is the process which determines the exact order of the three billion chemical building blocks made up of the four different bases: Adenine, thymine, cytosine and guanine – the order of the bases on a DNA strand is the DNA sequence.

Is human and animal science linked?

Yes.
The speed of progress in biotechnology, science, statistical techniques, computing power and the understanding of DNA in dairy cows is closely linked to the progress medical science has made in understanding human DNA.

In the year 2000 the first full sequence of a human genome was completed. Each of us has the human genome, and the majority of markers are the same, however, we all have differences, and it is the mapping or identifying the differences which are important.

Like humans, all dairy cows have approximately 3 billion base pairs within the genome – some species have less, others have more.

What are SNPs?

An entire set of 30 pairs of bovine (or 23 pairs of human) chromosomes is called a genome. Sometimes when a genome is copied to make a new cell, mistakes are made.
SNPs – Single Nucleotide Polymorphism – are the copy errors.

It is the SNPs which account for genetic differences in, for example, appearance, susceptibility to disease and responses to drugs/medication

What do the differences in markers show?

The differences can have significant effects, for example they determine eye colour, disease and height variations – some genes have no effect on specific traits, so by understanding markers we can identify those genes responsible for variations or differences.

So how does the progress made in understanding the human genome translate to the dairy cow?

Once the technology and machines had been designed and developed for sequencing the human genome, it made sense to do something else with them.

The same technology was initially used for sequencing other primates, for example apes, for comparative reasons.

Then in the mid 2000s funding was made available for researching the bovine genome, and work began at the Baylor College of Medicine in Texas.

Who invested in bovine genomic research?

In addition to funding from the US Government, a number of New Zealand dairy and agricultural organisations/industries contributed towards the work being done. This sent a significant signal to those investing in the work and resulted in securing funding for a number of years.

It was through the work carried out in the Texas lab that variations in bovine genome were first identified.

Four to five years after developing technology for sequencing and genotyping to map the human genome, scientists were able to leverage off the same technology and advances, and apply them to the bovine genome.

How did LIC utilise these advances?

LIC looked at the DNA patterns of Daughter Proven superior bulls with specific traits to determine markers they had in common.

It then looked at the DNA of unproven bulls to identify those that also displayed those favourable markers or patterns within their DNA.

The more favourable markers identified in the unproven bull the better that bull will be for that desirable trait.

LIC began investing in biotechnology in 1993 and were one of the first, of a very few companies to commit to this type of research, so at the time went way out on limb - investing several million dollars each year and uncertain of how it would realise a return on investment, but LIC made the investment, and it’s paid off.

Using DNA how does LIC identify young bulls by their genetic merit?

When DNA technology was initially introduced for use in bovines it cost between $2 and $2.50 to genotype just one or two marker variations in the bovine animal.

BUT almost overnight the ability to identify markers jumped to 10,000.

Equally significantly the cost to do this dropped to just one or two cents per marker.

The advances LIC had made meant, a couple of years later in December 2007, that LIC could identify 50,000 markers in the bovine DNA.

Now, LIC has a new panel which allows it to identify approximately 750,000 markers.

Over five years the ability to identify markers within the bovine genome has jumped from 10,000 to 750,000 - a dramatic improvement in the quality of information with very little change in costs per panel.

Markers are spread across three billion base pairs. The huge increase in identifiable markers enables LIC, with an even greater degree of accuracy, to identify the gene responsible for variations – for example in protein percentage.

DNA markers are not always the gene of interest, but markers that are close to the gene itself can be used as a surrogate.

Why is the identification of more markers important?

With the smaller number of markers there is a lesser degree of accuracy as identified markers are potentially further away from the actual gene of importance.

With fewer markers we are not fully equipped with the full story for identifying important genes.

By increasing the density of markers to 750,000 LIC has a greater degree of reliability and ability to identify markers close to the important gene.

Now LIC can select an animal, evaluate its breeding worth by using a panel of 750,000 markers and provide 55%-65% reliability compared to 80%-85% reliability for daughter proven.

In comparison a bull that young, with no DNA profile would provide only a 30-35% reliability.

What does LIC do with the DNA information?

By identifying which DNA patterns produce superior desirable traits, LIC can take a blood/tissue sample, look at an animal’s genetic profile and identify whether or not it is a superior animal.

DNA technology is adding significant accuracy to evaluations, so much so that bulls can now be used as one year olds.

Identifying superior bulls at a young age is important to New Zealand dairy farmers as by identifying superior sires and using them as one year olds the rate of genetic gain is increased by 30% to 40%; in the past we had to wait five years until sires were daughter proven.

When was genomic technology available to New Zealand dairy farmers?

In 2008 LIC commercially launched DNA Proven genetics to the market.

It has been heralded as the biggest advance in genetics since artificial breeding was developed more than 50 years earlier.

What are the expected benefits of genomic selection?

By utilising the science of genomic selection and the ever increasing knowledge and understanding of DNA sequencing and mapping, DNA technology promises to increase the rate of genetic gain in the dairy industry by 15-17 Breeding Worth (BW) units every year – in comparison to 10-12 BW without it.

Utilising DNA technology, HAZAEL VA RAZZLER-ET S2F (a son of VALDEN HI APPLAUSE-ET S2F) with a BW of 337/64 was eligible as a one-year-old to join the 2010 DNA Proven Premier Sires team; under traditional Daughter Proving farmers would have to wait until 2014 before introducing his genetics to their herd.

Can DNA be used to confirm parentage?

Yes
LIC has been utilising DNA information for parentage verification since the early 1990s, based around variations found in the genome called micro-satellites.

Initially it was possible to look at around ten DNA markers or variations to confirm parentage and, at that time, this was an effective method of parent identification – however, that was when the average dairy herd was between 200 and 250 cows and farmers routinely identified calves born and cows calved on that day.

The ability to use DNA to accurately confirm parentage has progressed in line with technology developments.

As herds got larger and those same levels of recording became more difficult for farmers, the early technology was no longer able to provide farmers with the accurate results they desired.

In the early 2000s, utilising the early work on the bovine genome LIC’s marker panel moved to a new platform (Generation 2), which was more efficient and provided more consistent results in the lab.

In the early 2000s LIC used between 30 and 40 SNP markers for parent identification which gave better accuracy for dairy farmers.

However, herd size continued to grow, from 350 cows in the average size dairy herd to 500.

Fortunately so did the advances in the science of DNA.

In the early 2000s the 50,000 marker SNP panel became available and, utilising this huge leap forward, LIC was able to genotype about 4000 animals.

Being able to DNA profile such a large number of animals provided LIC with the ability to identify which markers were suitable for parentage confirmation.

LIC was able to take the best of those 50,000 markers to more efficiently and effectively confirm parentage.

How does LIC utilise DNA science for parentage identification today?

With the best markers selected from the 50,000 marker SNP panel, LIC had three times as many markers that were in the previous parentage panel, so moved to the Generation three (G3) GeneMark product. This removed any previous reliance on recorded birth date for calves.

LIC tested the G3 platform on herds of more than 2000 to 3000 cows under scenarios with no MINDA records and no date of birth on calves and found the G3 panel performs exceedingly well.

LIC has a high degree of confidence that even with the growth of herd size this panel is future proof.

Parentage identification benefits dairy farmers

It costs about $1000 to rear a calf to enter the herd. Given the costs it is therefore important farmers know they are rearing the correct animals, ensuring the calf is AB bred and has correct parentage.

Farmers using the G3 technology have around 97% of their animals allocated correctly to both sire and dam.

Those who do not fully utilise DNA technology are expected, on average, to miss-identify approximately 15%-20% or even higher of their herd - a known statistic in New Zealand dairy herds.

Is G3, the ‘b-all and end-all’ of parentage testing?

The G3 GeneMark product means farmers can rely solely on a DNA profile to identify parentage, to both sire and dam.

The technology GeneMark has now developed is so accurate it means there is no need to develop another wave of technology to increase parentage matching rates – the level of technology LIC is currently using for parentage testing is here for the long term.

So yes - G3 is the b-all and end-all. There will not be another platform and there will not be another migration, more gene information may be added in the future but farmers can be confident that they will not need to re profile or migrate.

Can DNA be used as a diagnostic tool?

In the future LIC expects to move towards using DNA as a diagnostic tool for dairy farmers.

There is already a number of diagnostic tests available for humans. People can access tests where their human DNA is genotyped for a number of genetic markers; tests can identify a genetic pre-disposition to cancer, obesity, high blood pressure, diabetes and number of other congenital conditions.

As more of the bovine DNA code is untangled, LIC expects to gain the knowledge needed to identify genes that influence additional traits of interest.

In time LIC expects to be able to offer farmers further tests in addition to parentage, for example, an early evaluation on cows for BW traits and traits outside of BW which indicate disease. Work has already begun into these areas and LIC is currently researching Johne’s and Feed Conversion Efficiency.

What is the future of genomics?

LIC is already utilising DNA technology to identify genetically superior bull sires.

In 2008 the company launched its DNA Proven product and, using the 50,000 SNP panel, has been able to accurately evaluate potential sires by mapping and identifying favourable and desirable markers/traits within the bovine genome.

The 2010 year saw advances which allowed 750,000 markers on a panel, taking accuracy of evaluations to a higher level again.

Using the 50,000 SNP technology LIC is currently operating at 55-60% accuracy in reliably estimating genetic merit.

LIC has genotyped a few thousand animals, but plans to increase this to between 15,000 and 20,000 animals.

With the introduction of the higher density 750,000 SNP panel and by screening a larger number of animals, reliability will increase to approximately 65%, however, LIC is hopeful that figure will be higher, and expects to see this in the near future.

Another technology revolutionising human genomics is sequencing, or the reading of each of the billions of individual base pairs in an animal’s DNA.

It took 10 years of work to sequence the human genome at a cost of $US2 billion; five years later, at a cost of $US50 million, the bovine genome was sequenced; today it costs about $US10,000 to sequence a human or bovine genome.

The rapid technological advances are so remarkable that LIC expects, given the DNA projects scientists are working on around the world, in the next two to three years people will be able to have their genome sequenced for as little as $US1,000.

The technological changes, learnings and advances progress with human DNA, will be mirrored with bovine DNA advances.

The changes and advances seen in 2000 around understanding the human DNA were an accumulation of 10 years research.

To put in context how fast progress has been, working on the first human genome took 10 years to sequence it – today it takes a matter of weeks, if not days to sequence a human genome.

What’s happening in the field of human medical studies is remarkable.

When people have a specific phenotype (disease), they are able to sequence their genome to identify which gene may have caused it. By identifying variations present within the gene it may be possible to identify the cause of the disease and identify medicines that may be effective in dealing with a genetic mutation those people have, and this technology is close to becoming routine in some hospitals.

In the future it will become routine for people to go to the doctors and have the ability to do genotyping tests where diseases are identified by their genetic effects.

As sequencing becomes cheaper, the challenge, however, will be how to deal with all the data that is generated.

How do these advances support the dairy industry?

As technological advances are made to progress the science which targets human DNA, the same advances are totally appropriate to bovine DNA.

LIC will be able to leverage off the work done into unlocking the human DNA to build the tools and resources necessary for its work into unravelling the bovine DNA.

In the middle of 2010 LIC started sequencing DNA from a number of bulls important to the New Zealand dairy industry and instead of having 750,000 variations mapped, the company it had between 10 and 15 million DNA variations on a selection of animals.

In the next four to five years LIC will have sequenced hundreds of animals – it will then be able to utilise its increased knowledge of genetic variations in bovine to enhance its DNA products.

Eventually every bull in the DNA Proven team may be sequenced before it is sold commercially.

Why is the human and bovine genome comparable?

The order of the human genome is relatively similar to the bovine’s. Evolutionally there is evidence that about 60 million years ago humans and bovines had a common ancestor. Today we share many similar variations and a lot of human and bovine genomic material is identical.

In six years human geneticists have gone from being capable of genotyping 100,000 markers in human DNA to 2.5 million.

With sequencing becoming relatively cheap it is not expected that we will see another jump in the number of markers that human geneticists use.

The money spent by governments and pharmaceutical companies around the world in the science on human genomics is HUGE and the services companies provide for genomic products are totally appropriate for what LIC is doing, so it is able to leverage off what they have invested to date.

DNA part of every day language

Fifteen years ago the word DNA meant very little to members of the general public. Awareness was more along the lines of it being a science, something studied in labs and not a widely known term – but today DNA is part of everyone’s vocabulary.

DNA is discussed routinely with human health, DNA forensics solve cases and crimes, provide answers, people falsely convicted of crimes in the past are exonerated today with DNA evidence, and our genealogy can be traced back to where our ancestors and bloodlines came from using DNA.

In some ways the technology we are using is getting closer and closer to the over- dramatised razz-ma-taz we see on TV programmes like CSI. The fact is that today the speed at which we are doing things, processing data and information and getting answers is not that far away from the fiction.

What do farmers want from DNA technology?

When speaking to farmers about the possibilities of where DNA could take us in the future, many have expressed an interest in identifying animals susceptible to certain diseases.

LIC believes that DNA will become more and more relied upon in dairy farming and that it will improve efficiencies - and also become a part of everyday life for farmers through future health services.