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For decades the human Y chromosome, the male sex chromosome, has been the Rodney Dangerfield of human genetics: "it don't get no respect." For long, the Y was considered to be little more than a smaller, less stable version of the X. Now, new evidence from Dr. Page and his collaborators at the Whitehead Institute, the Massachusetts Institute of Technology, and the University of Washington reveals that the Y chromosome has led an independent existence after all.

Familial hypercholesterolemia, a genetic disease characterized by high levels of cholesterol and early mortality, is caused by defects in the receptor for the low-density lipoprotein (LDL)—the bad cholesterol. Now, Boston area scientists have found that this occurs because mutations in the LDL receptor prevent the protein from folding into its normal shape. This in turn impedes the receptor's ability to bind bad cholesterol and remove it from the bloodstream, causing the hypercholesterolemia.

For the first time, scientists have isolated embryonic tissue from zebrafish and successfully grown the tissue in culture. This assay will offer scientists a long-sought and powerful research tool, allowing them to study early development in ways that are not possible with other model organisms like frogs, mice, or chicks. Using this culture, the scientists also found key genes involved in the formation of the zebrafish nervous system.

Scientists have found that a specific defect in the male sex (Y) chromosome, known to cause azoospermia, or the inability to make sperm, can also cause the most common form of male infertility-low sperm production, or oligozoospermia. This study is the first to definitively show that genetic defects can cause low sperm counts in some males and suggests that intracytoplasmic sperm injection (ICSI)—the now popular technology of injecting a single sperm into an egg to circumvent low sperm counts—may cause the sons of these men to inherit infertility.

Dr. Rudolf Jaenisch, a Member of the Whitehead Institute for Biomedical Research, and Dr. Mario Capecchi from University of Utah in Salt Lake City have received the prestigious Molecular Bioanalytic Prize from the Boehringer Mannheim Group in Germany. In awarding this prize, the Group cited the scientists' pioneering work in establishing transgenes as a basic tool for research in molecular biology and medicine.

The Whitehead/MIT Center for Genome Research has received a three year, $26 million grant from the National Institutes of Health (NIH) to begin sequencing specific portions of the human genome. The Center's effort, along with others in the country, launches the final and most important phase of the Human Genome Project-decoding the exact sequence of the 3 billion DNA letters that make up the human being. Ultimately, sequencing the genome will help researchers identify disease-related genes and result in unprecedented advances in health care.

Scientists at the Whitehead Institute for Biomedical Research have achieved a major goal of the international Human Genome Project with the completion of the world's first comprehensive genetic map of the mouse genome. The mouse map appears in the March 14 issue of Nature along with a comprehensive genetic map of the human genome created by researchers at Genethon in France.

Circumventing a long-standing problem in drug design, scientists have developed a novel way to identify a new class of protein building blocks that could serve as valuable leads for drug development. The new method, called mirror-image phage display, represents an important advance in the rapidly growing field of drug-design. It will also offer new insights into the structure and function of important proteins.

Researchers at the Whitehead Institute for Biomedical Research and Boston's Children's Hospital have found a new way to rev up the engines of the mammalian immune system. They have taken an organism used worldwide to vaccinate against tuberculosis and packaged inside it mammalian genes that stimulate immune cell function. This achievement could lead to more effective vaccines for a broad range of human diseases and also-because the same organism is used in immunotherapy for bladder cancer-to safer, more effective cancer therapy.