Hundreds of random mutations in leukemia related to aging, not cancer
Hundreds of mutations exist in leukemia cells, but nearly all occur randomly as a part of normal aging and are not related to cancer, new research shows. In many cases only two or three additional genetic changes are required to transform a normal blood cell already dotted with mutations into acute myeloid leukemia (AML) – a blood cancer that develops when too many immature blood cells crowd out healthy cells.
Each AML patient’s leukemia cells hold hundreds of mutations. However, each stem cell acquires about 10 mutations per year. By age 50, a person has accumulated nearly 500 mutations in every blood stem cell. “These random, background mutations occur during cell division and are unrelated to cancer. Our DNA can tolerate a huge number of these hits without any negative consequences. But if a cancer-initiating event occurs in one of these stem cells, it captures the genetic history of that cell, including the earlier mutations, and drives leukemia to develop,” says research co-first author Daniel Link.
The genomes of 24 patients with AML were sequenced, and mutations in their leukemia cells were compared to those in the blood stem cells of healthy individuals. Surprisingly, the total number of mutations varied by age, not by whether a patient had leukemia. So a healthy person in his 40s had about the same number of mutations in his blood stem cells as a leukemia patient of the same age had in his cancer cells. The results help explain why leukemia occurs more frequently as people age. “It is the persistent, random accumulation of mutations in blood stem cells that contributes to the risk of the disease,” says co-first author John Welch.
13 novel “driver” mutations that likely help leukemia to develop were identified, along with a number of additional cooperating mutations that work with the driver mutations to give blood stem cells a growth advantage over other cells. In addition to an initiating driver mutation, apparently only one or two cooperating mutations were important for cancer to occur.
Eye color is typically taught as a basic Mendelian trait when we learn about genetics, one controlled by a single gene that we can map out on a punnet square. According to a study published on Nature’s Journal of Human Genetics, this is simply not the case. Of the 16 genes responsible for eye color, the two main genes illustrate epistasis, as “An intron in HERC2 contains the promoter region for OCA2, affecting its expression.” Epistatic interactions can contribute to differently colored eyes (heterochromia iridum), as well as the absence of pigment in the eyes (ocular albinism).
Photo Credit: Suren Manvelyan Photography
(Source: nature.com)
Thank you mitchellmoffit for the above video submission:
In honour of Father’s Day - a simplified overview of cancer (namely, prostate cancer).
Proteus Syndrome, or Wiedemann syndrome, is a congenital genetic disorder that occurs during embryonic development causing overgrowth in certain cells.
Credit:Darryl Leja , NHGRI
Development of eyes on a fruit fly leg from ectopic expression of the “eyeless” gene.
The Pax6 gene, known as eyeless in the fruit fly family Drosophilia, is typically considered the “master control” gene for eye development. The gene functions identically, if not highly similarly across animal species - in humans and rats, the amino acid sequences for the gene are 100% identical. More interestingly, the human/mouse version of the gene, while coding for a different sequence, functions normally in Drosophilia.
This gene also yields some unique ectopic results. As photographed in the above image, when the eyeless gene is inserted to a stretch of DNA coding for leg development, eyes develop on the leg of a Drosophilia fruit fly.
Sources:
http://dev.biologists.org/content/124/23/4819.full.pdf
http://www.dnalc.org/view/16772-Gallery-37-Drosophila-eyeless-mutant.html
http://en.wikipedia.org/wiki/PAX6#cite_note-pmid10461206-3
This peacock illustrates the genetic concept of codominance, allowing both the wildtype and albino phenotypes to be expressed for feather color.
Genome of Monozygotic Twins Discordant for Multiple Sclerosis
Multiple Sclerosis is a crippling neurological disease described as the following:
A nerve disorder caused by destruction of the insulating layer surrounding neurons in the brain and spinal cord. This insulation, called myelin, helps electrical signals pass quickly and smoothly between the brain and the rest of the body. When the myelin is destroyed, nerve messages are sent more slowly and less efficiently. Patches of scar tissue, called plaques, form over the affected areas, further disrupting nerve communication. The symptoms of MS occur when the brain and spinal cord nerves no longer communicate properly with other parts of the body. MS causes a wide variety of symptoms and can affect vision, balance, strength, sensation, coordination, and bodily functions.
-Gale Encyclopedia of Medicine
A 2010 study published on Nature has found that Multiple Sclerosis is not entirely genetic-based. Using twins, the study found that the concordance of MS in monozygotic twins (identical twins, share 100% of their genome) was only 35%. The concordance between regular siblings dropped to a mere 5%. While there is a genetic correlation, it’s polygenically actuated with environmental influence.
