New data, generated by Hongbing Shen and colleagues, at the Cancer Center of Nanjing Medical University, People’s Republic of China, has identified a genetic variation that seems to help predict survival in individuals with non–small cell lung cancer (NSCLC).

A systematic screen of the DNA carrying the information for generating regulatory RNA molecules known as a microRNAs identified a specific genetic variant that was associated with decreased survival in individuals with NSCLC.  The specific genetic variation resulted in increased levels of expression of the functional miRNA molecule.  This was not because more of the miRNA was made but because more of the precursor form of the functional molecule was processed to become functional.  The functional miRNA molecule generated by the genetic variation also had different functional properties.  The authors hope that further characterization of genetic variations that modify miRNA expression and/or function will uncover other indicators of survival and opportunities for developing new therapeutics.

What are the genes implicated in upright walking of humans? The discovery of four families in which some members only walk on all fours (quadrupedality) may help us understand how humans, unlike other primates, are able to walk for long periods on only two legs, a scientist will tell the annual conference of the European Society of Human Genetics tomorrow (Monday 2 June).The quadrupedal families in Turkey previously attracted attention in 2005, when they were discovered. Now the Turkish team reports that they have found the first gene implicated in quadrupedal locomotion in these families.

Professor Tayfun Ozcelik, of Bilkent University, Ankara, Turkey, and colleagues, studied four unrelated families where some members were affected by the rare quadrupedic condition, Unertan syndrome, which is also associated with imperfect articulation of speech, mental retardation, and defects in the cerebellum, a part of the brain involved in motor control. They found that the affected individuals in two families had mutations in the gene responsible for the expression of very low density lipoprotein receptor (VLDLR), a protein which is known to be critical to the proper functioning of the cerebellum during development.

Although the families lived in isolated villages 200-300 km apart and reported no ancestral relationships, the scientists expected to find a single genetic mutation implicated in the condition. They were surprised to find that this was not the case.

“We carried out genome-wide screening on these families”, said Professor Ozcelik, “and found regions of DNA that were shared by all those family members who walk on all fours. However, we were surprised to find that genes on three different chromosomes are responsible for the condition in four different families.

“In families A and D there were mutations in VLDLR on chromosome 9, and in family B the phenotype maps to chromosome 17 to a region that contains at least 157 genes, and we are still looking for the precise mutation. Neither region appears to be implicated for family C.”

In all cases, the affected individuals were the offspring of consanguineous marriages, which suggests that if they had married outside the family they would not have had the condition. All of them had significant developmental delay in infancy. “Whereas normal infants make the transition to walking on two legs in a relatively short period”, said Professor Ozcelik, “these individuals continued to move on their palms and feet and never walked upright. Although they can stand from a sitting position and maintain this upright position with flexed hips and knees, they virtually never initiate bipedal walking on their own.”

It has been suggested in the past that lack of access to medical care exacerbated the effects of an under-developed cerebellum, and that this led to quadrupedality. “Although it may be true that family B lacked proper medical care, families A and D had consistent access to good medical attention, and both families sought a correction of quadrupedality in their affected children”, said Professor Ozcelik. “Indeed, an unaffected member of family A is a physician, who has been actively involved in the medical interventions. In addition, the parents in family A also discouraged their affected children from walking on all fours, to no avail. We think that social factors are unlikely to be involved in the development of quadrupedal locomotion.”

Mutations causing VLDLR deficiency are also found in Hutterites, a group of Anabaptists who live in colonies of North America. There, however, most of the affected individuals cannot walk at all. The neurological characteristics of the affected members of the Turkish families and the Hutterites seem similar, with the most striking difference being that the Turkish individuals are able to walk on all fours, said the scientists. They hypothesize that the Hutterites may be more profoundly affected due to the deficiency in VLDLR and a neighbouring gene, and therefore lack the motor skills even for quadrupedal locomotion.

Along with brain enlargement, speech, and the ability to make tools, upright walking has long been regarded as one of the key traits that have led to modern humans. Professor Ozcelik’s team have opened a window on how mutations in VLDLR affect brain development and influence gait in humans.

“It will be interesting to see if the VLDLR gene is involved in other types of cerebellar ataxias. In addition, we hope to identify the defective genes associated with quadrupedal locomotion in families B and C”, he says.

Researchers from the University of Melbourne, Australia, and the University of Texas, USA, have extracted genes from the extinct Tasmanian tiger (thylacine), inserted it into a mouse and observed a biological function – this is a world first for the use of the DNA of an extinct species to induce a functional response in another living organism.

The results, published in the international scientific journal PLoS ONE this week, showed that the thylacine Col2a1 gene has a similar function in developing cartilage and bone development as the Col2a1 gene does in the mouse.

“This is the first time that DNA from an extinct species has been used to induce a functional response in another living organism,” said Dr Andrew Pask, RD Wright Fellow at the University of Melbourne’s Department of Zoology who led the research.

“As more and more species of animals become extinct, we are continuing to lose critical knowledge of gene function and their potential.”

“Up until now we have only been able to examine gene sequences from extinct animals. This research was developed to go one step further to examine extinct gene function in a whole organism,” he said.

“This research has enormous potential for many applications including the development of new biomedicines and gaining a better understanding of the biology of extinct animals,” said Professor Richard Behringer, Deputy Head of the Department of Molecular Genetics, M.D. Anderson Cancer Center, at the University of Texas, who is the corresponding author on the paper.

The last known Tasmanian tiger died in captivity in the Hobart Zoo in 1936. This enigmatic marsupial carnivore was hunted to extinction in the wild in the early 1900s.

Researchers say fortunately some thylacine pouch young and adult tissues were preserved in alcohol in several museum collections around the world.

The research team used thylacine specimens from Museum Victoria in Melbourne Australia to examine how the thylacine genome functioned.

The research team isolated DNA from 100 year old ethanol fixed specimens. After authenticating this DNA as truly thylacine, it was inserted into mouse embryos and its function examined.

The thylacine DNA was resurrected, showing a function in the developing mouse cartilage, which will later form the bone.

“At a time when extinction rates are increasing at an alarming rate, especially of mammals, this research discovery is critical,” says Professor Marilyn Renfree, Federation Fellow and Laureate Professor in the University of Melbourne’s Department of Zoology, the senior author on the paper.

“For those species that have already become extinct, our method shows that access to their genetic biodiversity may not be completely lost.”