Mapping the Suri Gene
Mapping the Suri Gene
Hello all. I thought I would send a progress report and a big thank you to all the alpaca breeders who generously donated blood samples from their animals for the Suri gene mapping project. My lab received one year of funding (of the 3-4 years needed) to begin mapping the suri phenotype. The suri phenotype clearly follows a single gene dominant pattern of inheritance in pedigrees. This means inheriting one copy of the suri allele (Ss) and you are a suri, two copies (SS) and you are a suri, no copies and you are a huacaya (ss). Phenotypically we cannot tell homozygous suris (those with two copies of the suri allele, SS) from heterozygotes (those with one copy of the suri allele and one of the huacaya allele Ss). It is valuable to suri breeders to know if the studs and dams they are breeding are homozygous or heterozygous, as two heterozygous studs bred together will produce huacaya offspring 25 of the time (on average). Homozygous suris will produce only suri cria. With this in mind I submitted a proposal to the Alpaca Research Foundation (ARF) in the USA to map the suri trait. I submitted a three-year grant, and was awarded a one-year preliminary award to get started. We will likely need 200-400 markers evenly distributed over the alpaca genome to detect linkage or genetic association, tested in 50-200 animals. To date, we have 42-50 markers typed in 100 animals and hope to fill in the missing data to bring it to 50 markers completed in 96 animals. We have applied for an additional year of funding to ARF to do the next fifty markers and will be applying elsewhere for the money to do the remaining 100-300 markers that will likely be required.
How does gene mapping work?
1. Basic Genetics: A little basic genetics must be explained first. Alpacas have 37 pairs of chromosomes (74 total in the nucleus of each somatic cell). One set of 37 chromosomes came from the dam in the egg, one set of 37 came from the sire in the sperm that fertilized the egg. Each sperm or egg only contains one copy or each of the 37 chromosomes, and it is random which of the two copies of each chromosome end up in each sperm or egg. The chromosomes themselves are made up of DNA. Between 2-5 of the DNA codes for proteins (DNA regions that code for proteins are called genes). The remainder is either junk DNA with no function, or control regions which direct the production of or action of proteins in cells. A good percentage of junk DNA in animals (humans and alpacas included) is made up of repetitive DNA sequences, wherein the same letters of DNA are repeated over and over again. These repetitive DNA regions evolve or mutate at a very fast rate, so they can be very useful for finding differences between even closely related individuals. One kind of repetitive DNA is called short tandem repeats (STRs). They are also called microsatellites. STRs consist of DNA patterns 2-6 letters long repeated tandemly. For example a dinucleotide repeat consists of two letters (CA) repeated over and over: CACACACACACACA (CA repeated 7 times, often denoted CA7). Individuals vary in how many times CA is repeated. Because everyone has two copies of each chromosome, most individuals will have a different number of repeats from the dam and from the sire on the two copies of each chromosome (CA7 from the dam and CA15 from sire for example). Sample another animal and it will often have two completely different sizes (Say CA9 and CA12). There are hundreds of thousands of these repetitive regions spread throughout the 37 chromosome pairs. The Alpaca Genome Project was devised to find STRs evenly spaced throughout the alpaca genome, and was completed in 2006. These are like mileposts along the chromosomes to give us locations (hence the term "map"). Warren Johnson at the National Cancer Institute generated these markers with funding by the Alpaca Research Foundation and the Morris Animal Foundation, and provided a list of them to the Merriwether lab at Binghamton University (State University of New York) for mapping traits in camelids. We began optimizing the markers for use with our alpaca samples in 2005 and have currently typed up to 50 in up to 100 animals.
2. How to map genes: Presumably when the mutation that created the suri fleece type occurred, it happened on just one chromosome in one animal thousands of years ago, and every animal with suri fleece alive today is descended at least in part from that animal. When the suri mutation occurred, it happened on a chromosome that already had many mutations along its length (the genetic background of that chromosome). This means that the suri mutation was initially "linked" to all these other mutations that were already there. The suri mutation and the older background mutations stay linked until "recombination" occurs to separate them. The closer two letters of DNA are together on a chromosome, the less likely recombination will happen between them to separate them. In this case, we are hoping to detect linkage or association between the letter change (mutation) that caused the suri fleece type and the number of STR repeats. If one of our 400 STRs is close enough to the suri fleece mutation, it will always be linked to it, and whatever allele the linked STR had when the suri mutation occurred, that allele will always be found in individuals with suri fleece. It does not cause the suri fleece. It is "linked" to it. So we look for allele sizes of STRs from all across the genome (an allele is just a variant of a stretch of DNA, different numbers of repeats are called different alleles too). You need to type a large number of STR markers to hope to find one that just happens to be right next to the gene that causes the phenotype you are testing for (a phenotype is the physical expression of a gene, the genotype is the genetic sequence that causes the phenotype). If there was an STR region (called a locus) right next to the gene that encodes the suri fleece trait, and it had 33 repeats (CA33) when the suri mutation occurred, then almost all suris will have 33 repeats in that STR locus as well. Unlinked loci that are not nearby the suri gene will be completely randomly associated with the numbers of repeats in their STRs and the suri trait. This is because the farther away you are from the gene you are looking for, the more likely recombination will separate the gene and the STR marker. Only those on the same chromosome and fairly close will remain "linked" together. The farther apart they are, the weaker the linkage, the lower the percentage of time the allele size and the trait will occur together. So the more markers you screen, the better chance one will actually be close enough to your gene of interest to be linked to it.
I know this is complicated to explain. I am enormously grateful to the alpaca community for supplying the blood samples from their animals so that we can map this trait and many others. We are currently trying to map the genes for Choanal Atresia, Wry Face, Polydactyly, Catarracts, the suri trait, and coat and skin color and pattern among others. We are also using a candidate gene approach to sequence genes involved in coat color and pattern in other species, sequencing the genes for the melanocortin-1 receptor, the agouti protein, agouti signaling protein among others. We can always use more blood samples. If you have a cria born with any defects, please retain a blood or tissue sample and send it to me. I would also like blood from any blood relatives of the animal with the defect (Dam, sire, and any other relatives you can connect via pedigree). You can email me at firstname.lastname@example.org, or call my lab at 607-777-6707 in the United States. The samples can be dried on FTA cards and mailed at room temperature to:
Dr. D. Andrew Merriwether Lab
Department of Biology
210 Science III Bldg
Binghamton, NY 13902-6000
I welcome samples from any camelids (Alpacas, Guanacos, Vicunas, Llamas, Bactrian and Dromedary Camels). Since we are mapping fleece style (suri or huacaya) and color and pattern, all animals are useful. It is helpful to have registration numbers for the animal and its parents to help build pedigrees. It is all strictly confidential. No one other than my lab will ever be able to connect any animal, blood sample or DNA sample to any farm, person, or trait.
D. Andrew Merriwether, Ph.D. is Associate Professor of Anthropology and Biology
Binghamton University. He and his wife, Ann, own Nyala Farm Alpacas, 104 Rockwell Rd, Vestal, New York 13850 USA