Anthropology.net

From Nobel Intent comes news of a discovery in the Mendelian genetics of Mirror Movements, a condition that causes people to involuntarily move both sides of their body when they intended to only move one.

Aside from being medically relevant, interesting on a population genetics level, and involved an Iranian family, it also caught my eye because about 3 weeks ago we covered the implications of DCC (deleted in colon cancer gene, I know — very clever!) mutations in my pathology course. DCC mutations are found in the sequence of events that lead up to a special type of familial adenomatous polyposis (FAP), known as Gardner syndromes.  These colon cancers occurs primarily on the left or descending colon. The morphology of FAP cancers lead to a napkin ring like constriction of the colon that present as alternating bouts of diarrhea and constipation. What makes them unique from other FAPs is that they have present with extracolonic manifestation, like bone cancers.

The DCC gene is on the long arm of chromosome 18. I know that it is a cell surface protein responsible for cell-to-cell and cell-to-matrix adhesion. Normally when cells proliferate, they squeeze up on each other and DCC works via contact inhibition to signal a stop in proliferation because conditions are getting too cramped. Therefore, if DCC is deleted, contact inhibition is lost and cell loses ability to proliferate, yielding a dysplastic growth.

Genbank classifies this gene as one that encodes for a netrin 1 receptor, which I did not know before I read this post. I find this really interesting in the relevance of DCC to Mirror Movements. Dr. John Nicholls,of SISSA in Trieste, Italy,  the dude for neurodevelopment, guest lectured my neuroscience course during my second term of medical school last year. I remember him describing netrins as a class of axon guiding proteins that functioned during growth and development. The hallmark experiment I remember him citing was the Oster, et al., 2004, where ganglion cell axon pathfinding in the retina and optic nerve was guided by netrin signals.

It seems that in Mirror Movements, the mutation in DCC prevents it from helping,

“nerve cells on one side of the spinal cord to stay on that side as they extend processes up and down the developing spine…. Because the protein is malformed, the body develops neural connections that route one-sided connections to both sides, producing the mirrored activity.”

I don’t have access to Science unfortunately to research the demographics of the particular SNP they discovered… So I can’t tell you of the gene frequencies… But if anyone does have access to the paper, and doesn’t emailing me, I’ll be very grateful. I love these sorts of discoveries where I learn something new and integrate what I’ve learned the past year and half of medical school!

Srour M, Rivière JB, Pham JM, Dubé MP, Girard S, Morin S, Dion PA, Asselin G, Rochefort D, Hince P, Diab S, Sharafaddinzadeh N, Chouinard S, Théoret H, Charron F, & Rouleau GA (2010). Mutations in DCC cause congenital mirror movements. Science (New York, N.Y.), 328 (5978) PMID: 20431009

Kambiz here. I’m about to start my second term of medical school, which is both exciting and nerve racking. In my summer readings, I came across a medical and anthropological tidbit today that caught my attention: redheads have a lower tolerance for pain. I didn’t know that.  Did you?

Skin pigmentation is one of my favorite topics. We know from previous posts that the melanocortin-1 receptor gene or MC1R affects melanin production and ultimately skin and hair phenotypes. Redheads carry a variant of MC1R which produces a different pigment, called pheomelanin, resulting in freckles, fair skin and ginger hair.

How MC1R receptors affect pain is another story though, one that is not well understood. Aside from the skin MC1R is also expressed in the brain. It could be possible that the redhead allelic variant of the MC1R receptors don’t quite receive the signal transduction of pain reception in the same manner as those with the wildtype receptor. I don’t think I’m gonna become an anthesthesiologist but as someone interested in human genetic variation it is good to acknowledge some phenotypes affect how medicine is delivered. ;-)

Anyways, I don’t have much else to add to this other than to share some interesting information and to let you all know I’m alive but will be crawling under a rock again. Till next time.

I’ve successfully completed my first term of medical school, and realized I have a lot of free time so I’ve decided to pick up blogging during my short summer break in order to prevent brain rot. Today, I noticed an interesting anthropology-medicine news bit pass by my RSS reader and wanted to share it with y’all. The paper behind the news announces the finding of the oldest evidence of leprosy in India, specifically the Balathal site nearby Udaipur in the state of Rajasthan, India. It has been published in the open access journal, PLoS ONE, under this title, “Ancient Skeletal Evidence for Leprosy in India (2000 B.C.).”

The significance of this finding is that it pushes the existence of leprosy back by 2,000 years, from biblical times, with physical evidence.

Balathal, Indus/Harappan Site in Rajasthan, India

The skeleton of this middle aged (37 or so years old) adult male was buried about 4,000 years ago during a time which Balathal was a large agrarian settlement at the margins of the Indus (or Harappan) Civilization. He displays:

• Erosive lesions at the supraorbital region and glabella
• Remodeling of the margin of the nasal aperture, including the anterior nasal spine,
• Bilateral necrosis of the infraorbital region of the maxilla
• Resorption of the alveolar region of the maxilla with associated antemortem tooth loss
• Pitting near the midline and in the alveolar region of the palatine process
• Root exposure, alveolar resorption, antemortem tooth loss to the mandible and a small apical abscess at the left lower third premolar
• Ventral wedging, osteophytosis, and ankylosis to the cervical vertebrae
• Periostosis to the left tibia

These are all characteristics of leprosy, treponemal infection, leishmaniasis, sinus and oral infections, tuberculosis, osteomyelitis and non-specific infection in the post-crania. But differential diagnosis ruled out all of the other pathologies other than leprosy.

The individual was excavated between 1994–1997. Lots of hallmarks in human existence occurred during this time period, some being inventions in system of writing, standardized weights and measures, monumental architecture, and trade networks that stretched to Mesopotamia and beyond. While the pathophysiology of leprosy is up in the air, it is not surprising that communicable diseases, even not very contagious ones like leprosy, also blossomed during the rapid sedentarisation of human populations.

The cranium of individual 1997-1

Leprosy is a granulomatous (nodule) disease of the peripheral nerves and upper respiratory tract mucosa, caused by immune system unsuccessfully trying to sequester the infectious bacterium Mycobacterium leprae and Mycobacterium lepromatosis. Unlike popular belief, body parts falling off is not the primary symptom of leprosy, but rather skin lesions are the main external manifestation of the disease. The damage to the nerves affects blood flow and ultimately causes necrosis of tissue, which happens in during the advanced lepromatous stages.

Anterior view of the mandible from individual 1997-1

What is curious is that descriptions of leprosy have been noted in Ebers papyrus, an Egyptian medical document and the Atharva Veda, a Sanskrit holy text, which both refer to the disease as early as 1,550 B.C., a few hundred years after this individual died. I wonder if this guy was one of the first Lepers then? Gwen Robbins, first author of the publication, expressed interest in recovering DNA from the Mycobacterium leprae and comparing it to strains common in Africa, Asia and Europe today in order to shed additional light on the origin and transmission routes of this disease, in fact she hypothesized that the disease migrated to the subcontinent from Africa, at a time when substantial interaction among populations throughout Asia, the Middle East, and Africa.

Elements demonstrating pathological conditions in the postcranial skeleton of individual 1997-1.

Robbins, G., Tripathy, V., Misra, V., Mohanty, R., Shinde, V., Gray, K., & Schug, M. (2009). Ancient Skeletal Evidence for Leprosy in India (2000 B.C.) PLoS ONE, 4 (5) DOI: 10.1371/journal.pone.0005669

In this 3 minute 44 second video, Pardis Sabeti discusses the future of genomics, i.e. how sequencing will become so cheap that personal genome sequencing will be ubiquitous. She also talks about the impact of sequence information on medical and human variation research as well as the necessary ethical precautions we need to take with this information. Check it out.

In my life, I’ve seen Christopher Columbus’ reputation take the downward spiral from hero to enemy. It has even affected me in a very superficial manner. See, even though the US government has commemorated the day he found the Americas as a holiday, I remember being devastated the year when my school district decided to nix the day off I was so looking forward too.

Since then, my education in anthropology hasn’t held him to a high standard either. He’s often vilified for starting the end of native American existence. And now a new study in PLoS Neglected Tropical Diseases, traces the emergence of syphilis in Europe to the time when Columbus returned from the Americas. Furthermore, a phylogenetic comparison of the syphlilis causes bacterium, Treponema pallidum, shows that it is a close cousin to the South American tropical disease yaws.

Actually for some time Columbus has been blamed for bringing syphilis to the East. But a skeleton of a man was found in north eastern Britain with signs of bone lesions similar to those causes by syphilis. Preliminary dates of this skeleton suggested that the man had died around 1442, exonerating Columbus for a bit. Here’s a link to that paper, ‘“The syphilis enigma”: the riddle resolved?‘

Since then, anthropologists re-evaluated the date and suggested that the fishy diet of the region somehow affected the dating technique, making the skeleton seem older than it is. With all this confusion over paleopathology and dating techniques, a genetic analysis of the Trepanoma bacterium seemed much more logical.

In order to conduct the study, 22 human samples, including two Yaws samples, were compared. Even though Yaws is not sexually transmitted (it is transmitted through skin contact), it was included because it is thought that South American variety is a good candidate for the source of the venereal disease. Since the bacteria are so fragile only some sections of the genome could be recovered, including 17 base pairs that ended up being diagnostic of the different Treponema. Through a SNP analysis, it was found that syphilis and South American yaws shared 4 identical base pairs. Not entirely convincing but the overlap with any other kind of Treponema was almost non-existant… A phylogenetic tree of the Treponema samples also showed that syphilis had evolved most recently of the bacterial strains studied, and by most recently we’re talking about 500 or so years ago.

Columbus’ crew is the only one known to have voyaged to the Americas during that time. And the first recorded epidemic of syphilis in Europe broke out among French troops in 1495, two years after Columbus returned from his first voyage across the Atlantic, which points the finger to him and his people. But, with our knowledge of how bacteria can share genes, I’m not entirely convinced it was him. Furthermore, a 4 base homology isn’t a lot.