Kidney Disease and African Sleeping Sickness

Natural selection can actually favor an otherwise harmful allele of a gene, if that allele somehow confers a survival advantage in some individuals and populations. The one textbook example of this phenomenon has always been sickle cell disease, a genetically inherited disease that results in deformed red blood cells and can lead to early death. Sickle cell disease is prevalent in persons of African ancestry because the allele that causes sickle cell disease also protects the person with that allele from malaria, a disease which is widespread in Africa.

Now there’s a second example of this phenomenon. Researchers have found that two different alleles for a gene involved in the production of a blood protein can; a) lead to kidney disease, and b) protect against the parasite that causes African sleeping sickness. Not surprisingly, the two abnormal alleles and the kidney diseases they cause are four to five times more common in African Americans than in persons of European descent.

Researchers are wondering how many other genetic diseases we’ll find that also confer protective advantages against certain infectious diseases. Researchers are also hoping to develop new treatments for African sleeping sickness that are based on the proteins these abnormal alleles produce.

Heritable, Non-Genetic Behavioral Patterns

Why do abused children grow up to be abusive parents? Why do people raised in lower socio-economic environments tend to have more long-term health problems? Why is it so hard for drug addicts to kick their habit?

For possible answers, behavioral neuroscientists are turning to a hot new field called behavioral epigenetics. Behavioral epigenetics is the study of inherited changes in behavior or gene expression that are caused by factors other than changes in DNA, i.e., that are epi- (Greek: over, above) genetics.

According to epigenetics theory, environmental factors such as the degree of nurturing (or lack of it) by one’s parents early in life can alter the chemical structure of DNA (specifically, the degree of methylation of DNA and its associated histones). This in turn affects how and when certain genes are turned on and off. In theory, such chemical alterations in DNA could last for multiple generations (i.e., be heritable) even though the nucleotide sequence of the genes themselves hasn’t changed.

So far, there’s very little evidence to suggest that epigenetic mechanisms influence human behavior, mostly because human brain tissue is not readily available for research. However, laboratory studies show that rats raised by less-nurturing mothers tend to be more prone to stress as adults and to exhibit increased methylation of certain genes. It’s worth keeping an eye on this developing field to see where it leads.

DNA Mutations Between Generations

How often do errors in DNA replication occur between generations – i.e., how many times are new mutations found in a child that were not present in a parent? These new mutations created between generations would represent a “human mutation rate”. Undoubtedly they would contribute to human evolutionary change.

The human mutation rate per generation has been difficult to measure, but several different laboratories have now come up with numbers that are remarkably similar. According to the most recent estimate, the answer is about 60 DNA nucleotide base errors per generation. That sounds like a lot, but given that there are 3 billion nucleotide base pairs (6 billion bases) in the DNA in a human cell, that’s just one error in every 100 million bases. DNA replication and repair mechanisms are remarkably accurate, it seems.

And that’s why human evolution has occurred so slowly, over several million years.

Living With Cystic Fibrosis

Sixty years ago, before doctors knew very much about cystic fibrosis, most children with the disease died before school age. Today people with the disorder are living well into their 30s. Today we know that cystic fibrosis is a genetic disorder and we know what causes the symptoms.

What we don’t have is a cure. Prolonging the life of cystic fibrosis patients is largely based on improvement of care, including medicines that alleviate some manifestations of the disease and physical therapy to keep the lungs clear. What works for one patient doesn’t always work as well for the next.

An effective tool in the improvement of care for cystic fibrosis patients has been the establishment of a national registry of patients. The registry, which is managed by the Cystic Fibrosis Foundation, currently collects and stores patient records from more than 100 cystic fibrosis treatment centers across the country. The pooled data has proven very useful in learning what works best for which kinds of patients, and why. It’s like having the collective experience of thousands of doctors right at your fingertips.

The concept of a using a national registry of patients to improve patient care has proven so successful that other patient groups are copying it.

That's One Small Step for Gene Therapy...

French researchers report that they have successfully used gene therapy to treat beta-thalassemia in a 19-year-old male patient. Beta-thalassemia is a genetic blood disorder in which a defect in the gene coding for the beta-globin chain of hemoglobin results in persistent and life-threatening anemia and dangerously high blood iron levels. Two years after the treatment, according to the researchers, the young man no longer needs regular monthly blood transfusions and appears to be in good health.

The French team has the approval of French authorities to treat more patients with the same inherited disorder. The hope is that someday they’ll be able to successfully treat one of the most common of all genetic blood disorders – sickle cell anemia.

Genetic Screening Tests

What a difference a decade makes. Back in 2000, most U.S. states screened newborn infants for just four genetic disorders. Today, all 50 states screen for at least 21 of the 29 serious genetic or functional disorders that the American College of Medical Genetics recommends for testing. The list includes cystic fibrosis, sickle cell anemia, hypothyroidism, phenylketonuria, and a host of other conditions so rare you’ve never heard of them.

A list of the screening programs and tests provided by all 50 states can be found on the National Newborn Screening and Genetics Resource Center website. For information about the recommended tests, go to the March of Dimes website.

Do Identical Twins Have Identical DNA?

It has long been thought that identical twins must have identical DNA, since they came from the same fertilized egg. The usual explanation for any observed differences between identical twins was that they were caused by environmental factors such as diet, exercise, or exposure to chemicals.

Now we know that the DNA of identical twins is not always identical. That's because as cells divide over and over again during normal human growth and development, some sections of the DNA are omitted accidentally once in awhile. Other sections of the DNA are duplicated unnecessarily. The result is that some somatic cells and even tissues and whole organs may have one to three copies of some genes, instead of the usual two. Such copy number variations occur rarely in all people, not just in identical twins.

It would be helpful to know whether copy number variations contribute to specific human diseases, and (out of curiosity) whether copy number variations contribute to the slightly different phenotypes of some "identical" twins.

Fair-Haired Neanderthals

Those who are particularly interested in genetics and human evolution might want to take a look at the article published online in Science last week (E-pub ahead of print: 10.1126/science.1147417) and the published news item related to it (Science 318:546-547, Oct. 26, 2007). The authors of the online research article report that Neanderthals have a particular gene mutation that suggests that at least some Neanderthals had pale skin and red hair. There’s still no indication that Neanderthals ever interbred with modern humans, though. Instead, it appears that the Neanderthals evolved independently toward more human features before they died out entirely.