Thursday, November 13, 2008

AIDs patient cured in Germany

A patient with both leukemia and HIV was cured in Berlin, by receiving hematopoetic stem cells (the basic cell that gives rise to all your blood cells) from a match who was CCR5-. First, the patient had intensive chemo- and radiotherapy, then received a bone marrow transplant.

There is a high risk for the patient with a 10-30% chance of death from having your immune system and bone marrow cells wiped out before the transplant. Still, this is fascinating.
NYtimes Article

Tuesday, November 11, 2008

Autistim, or Schizophrenia?

According to Dr. Crespi and Dr. Badcock (thrilling surname!), epigenetic gene silencing of the father's versus the mother's genes may tilt a person more toward autism or more toward schizophrenia (NYTs article, Nature essay). Epigenetics is the term that describes changes to the genome that change which genes are expressed but do not change the genome itself. In general, methylation, the adding of a CH3 group to the 5 carbon of the nucleotide cytosine in a promoter, silences the expression of a gene, while demethylation or acetylation (tagging with a -CoCH3 group) increases expression. When a section of a genome is silenced depending on a parent's gender, that is called imprinting. As we all carry two alleles (one variant of a specific gene) total, one from each parent, when our sperm or eggs are being made only one of each of our alleles gets put into the sperm or egg. With a few genes, a paternal allele in an egg should be silenced, and a maternal allele in a sperm should be silenced (with many genes, both alleles are expressed in the baby). When the sperm and egg come together, there are two alleles, with one or the other silenced through imprinting. The proposed theory of mental health suggests a paternal allele in the mother that should have been silenced results in reduced social skills, and the expression of a maternal allele in the father that should be silenced results in emotional problems. So, too much paternal expression creates social ineptitute, and too much maternal expression makes crazy harpies?

At times a mis-expression of an allele is indeed a problem, as an example, consider Prader Willi and Angelman syndrome. A specific region of chromosome 15, designated as 15q11-13, is responsible for both conditions. In this section of the genome, alleles from both the paternal and maternal lines should be expressed. In Prader Willi, either the father's gene is silenced or two copies of the mother's are mistakenly passed along: an imbalance in favor of maternal genes. In Angelman, the maternal gene is silenced or two copies of the paternal alleles are passed along: an imbalance in favor of paternal genes. According to the article, the two syndromes result in very different behavior, more compliance in Prader-Willi's, and more hyperactivity in Angelman's, although from the description in my genetics book, both conditions present unique challenges and temper tantrums.

The article also suggests that mother's have, through evolution, silenced genes that result in difficult offspring, silencing any paternal genes that pass through into their eggs. Both articles reference the IGF2 gene, responsible for growth of the baby in the womb. Apparently this gene is expressed in the sperm and imprinted in the egg. If both alleles are expressed, the baby is 50% too big and hard to deliver, if neither is expressed, the baby is too small. It so happens the father's is expessed, resulting in typical fetal growth. What if the imprinting was simply reversed, silenced in the father and expressed in the mother?

While Badcock and Crespi propose an interesting theory, I am not sure the evolutionary interpretation holds much weight. A child with autism or schizophrenia can both present a great challenge, and in the accepted discrepancy in imprinting resulting in Angelman or Prader Willi, this is also true. So imprinting and epigenetics are being shown to cause behavioral and physical phenotypes, but the interpretation that places where the maternal alleles are imprinted may be due to ease of child birth and child rearing has only subjective speculation to back it up.

I believe I have heterogenous imbalances, as I am of late both social inept and emotionally hypersensitive and blissfully living in a state of self-deception. But I'm finally doing well in medical school, in genetics and neoplasia.