Tools for investigating Birth Defects

D. Andrew Merriwether Ph.D.

At some point in their lifetime everyone is likely to be faced with having a cria (or human child, friend, or relative) born with some kind of congenital anomaly. We immediately want to find out everything we can about this new problem. Hopefully your veterinarian or physician can put a name to the anomaly, and maybe even give you some information on its possible causes. In camelids we probably just don’t know the causes of most defects yet. In this case, our best bet is to look up the same thing in other species, including humans. So how do we do this? Below I will list the tools I like to use to get started.

Looking up a trait:

For this example I will use anal atresia (atresia ani), which is the lack of an opening for the anus, usually caused by a membrane covering the opening. This is a problem that crops up again and again in the North American alpaca herd. I have been told by Peruvian colleagues that it is so common in the Andes that shepherds carry a pen knife, needle and thread to cut the membrane and sew it open in newborns. This is often all that is needed for the animal to be able to grow up and prosper. For the shepherd, it means the cria lives and can go on to a career making fleece, fertilizer, offspring, and eventually meat, instead of being a complete loss. It does have the undesirable effect of increasing this trait in the gene pool if it is genetic and heritable. So how do we find out about it?

NCBI

Use the National Center for Biotechnology Information (NCBI) site (http://www.ncbi.nlm.nih.gov/). The National Institute of Health (NIH) and the National Library of Medicine (NLM) maintain this site and continually add cross-referenced search tools. Near the top of the screen, there is a drop-down Search menu that says " All Databases" as the default. If you type in "Atresia Ani" and hit return, you get a big window of all the databases and how many hits in each. In this case I found the following:

The search returned 1989 matches in Pub Med, 132 in PubMed Central, 1 in Site Search, 1 in OMIM, 7 in OMIA, etc….. What does all this mean? This search found all documents in these databases that had the letter combinations of both "atresia" and "ani" in the same document, but not necessarily together or in that order. You can refine the search by putting "quotes" around the words so that they have to appear together in that order as is shown below.

We see the 61 matches below. Now we see only 61 hits in PubMed and 88 in PubMed Central, etc.. You can restrict your search just to any one of these databases using the dropdown menu. So what are the databases? I will list the ones most useful to alpaca breeders here. PubMed is the public version of Medline, an immense database of journal publications that lists the reference and abstract for every article. PubMed Central is like Medline, but also includes the free full text of all the articles. OMIM is the Online Mendelian Inheritance in Man, a list of all potentially genetic diseases and traits in humans, with descriptions of each and what is known genetically about each and full bibliographies of each disease. OMIA is Online Mendelian Inheritance in Animals, and is the non-human equivalent of OMIM. Nucleotide is a search of Genbank, and searches the annotations of every sequence in Genbank (annotation is the written descriptions of the entry). Protein is a search of the protein databases, again by annotation. Not part of the dropdown menu, but part of NCBI, is a BLAST search, which searches using a sequence, so if you want to find what a piece of DNA does, BLAST it and see what it matches and what the matching DNA does.

So lets look just at PubMed.

We see #6 looks interesting. A mechanism for how it happens in pigs. Clicking on the link takes us to the online journal and to a link to view as HTML or PDF. I chose .pdf and the paper below appeared on my desktop. I have access to many journals free from my library at my University. You may get access to some from your local library or university library. If not the journal gives you the option of buying the article (usually for an obscene $20-$30. PubMed Central lists free online copies.

Looking in OMIA, we actually find a reference for atresia ani in alpacas.

This one was not available to me online, so I had to request it by interlibrary loan. At my university we have something called Illiad that sends me a .pdf file of the article that is made at another library by scanning it and emailing it to my library. Most libraries have interlibrary loan agreements so that you can get articles from journals they don’t carry. Looking under pigs we see that this disorder is definitely familial, but in pigs must be caused by more than one gene. Gene mapping in pigs finds two primary loci, and this article is available for free online.

Google Scholar

Another simple tool for looking for information is the familiar Google search engine (http://www.google.com) , found in most web browsers. Searching with Google finds all web sites and web documents and photos with the search terms in it. Again, putting "quotes" around "Atresia ani" restricts it to finding both words together in that order.

This also finds the Mechanism paper we found in PubMed (indeed that is where the Google link takes us). Many of the other finds are websites. If we want articles from books and journals, we should use Google Scholar, which you can find by hitting the more button at the top of the search window and choosing Scholar. Your best bet for accurate information is to stick to peer-reviewed journals, like those found in PubMed, and often in Google Scholar. Anyone can write anything and post it on a web page. That does not make it true, correct, or reasonable. Articles in peer reviewed journals are sent out for review by experts to make sure they are valid and the conclusions are supported by the data. Most papers are rejected, or at least made to be revised and resubmitted to fix problems with the papers. The Google Scholar results include some very useful papers.

We see most of these articles describe atresia ani as being genetic, and animals from sheep, swine and cattle breeding programs producing these problems are culled. You will also see that a number of articles discuss a lack of retinoic acid or folic acid as possible causes of atresia ani, so there are some possible environmental causes or triggers of this case in other species as well. \

So play around with these tools. They work for any species. All the species of the world share large parts of our genomes in common. We have many of the same genes a fruitfly or a dog has. If the trait you are looking for has been explained in another species, it may give us clues about the causes in our animals (or ourselves).

Andy Merriwether

Departments of Anthropology and Biology
Binghamton University
Lab: 607-777-6707
andym@binghamton.edu
and
Nyala Farm Alpacas
104 Rockwell Rd
Vestal, NY 13850
www.alpacastreet.com/nyalafarm.asp