Sunday, January 06, 2008
A simple, elegant paper published in Science maps a certain type of dwarfism to the PCNT gene:
Using genetic linkage analysis, we find that biallelic loss-of-function mutations in the centrosomal pericentrin (PCNT) gene on chromosome 21q22.3 cause microcephalic osteodysplastic primordial dwarfism type II (MOPD II) in 25 patients. Adults with this rare inherited condition have an average height of 100 centimeters and a brain size comparable to that of a 3-month-old baby, but are of near-normal intelligence. Absence of PCNT results in disorganized mitotic spindles and missegregation of chromosomes.Perhaps the goal of genetics is to understand how genetic information becomes an organismal phenotype; I find this example fascinating. It appears that cells lacking pericentrin have abnormal chromosome segregation, which leads, in some fraction of cells, to arrest of the cell cycle and possibly cell death. Now as this happens from birth, the authors propose simply that fewer cells=smaller stature. It seems rather intuitive, but this is biology--intuition is not always the best guide to reality, and it's fun when things make sense.
The authors note that a number of genes involved in microcephaly (ie. ASPM, MCPH1, etc.) are also involved in cell division. There's not much comment on this, but it does make sense these sorts of phenotypes (small stature, small brain) be affected by the rate at which cells divide or die.
Finally, having put together this nice paper, the authors take the well-deserved liberty of a little speculation:
There is an ongoing debate as to whether the Late Pleistocene hominid fossils from the island of Flores, Indonesia, represent a diminutive, small-brained new species, Homo floresiensis, or pathological modern humans. We note that individuals with MOPD II have several features in common with Homo floresiensis, including an adult height of 100 cm, grossly normal intelligence despite severely restricted brain size, absence of a sloping microcephalic morphology, and a number of minor morphological features including facial asymmetry, small chin, abnormal teeth, and subtle bony anomalies of the hand and wrist. Given these similarities, it is tempting to hypothesize that the Indonesian diminutive hominids were in fact humans with MOPD II. With the identification of the genetic basis of MOPD II, this hypothesis may soon be testable.