-The exome is the part of the genome formed by exons, the sequences which when transcribed remain within the mature RNA after introns are removed by RNA splicing.
-A “mutation” is also used as a noun to refer to the changed gene. Once a gene mutates, the change is passed on when the cell that contains it divides. If the change is in a sperm or egg cell that becomes a fertilized egg, it is passed to the next generation.
-Mutations can also help. For example, a mutation makes a person’s cells unable to manufacture a surface protein that binds HIV. These people are resistant to HIV infection.
– Many mutations have no visible effect because they do not change the encoded protein in a way that affects its function, just as a minor spelling error does not obscure the meaning of a sentence.
-Twenty-two pairs are autosomes, which do not differ between the sexes.
-The autosomes are numbered from 1 to 22, with 1 the largest. The other two chromosomes, the X and the Y, are sex chromosomes. The Y chromosome bears genes that determine maleness.
– Charts called karyotypes display the chromosome pairs from largest to smallest.
– The more factors that contribute to a trait or illness—inherited or environmental—the more difficult it is to predict the risk of occurrence in a particular family member.
-The bone-thinning condition osteoporosis illustrates the various factors that can contribute to a disease. Several genes confer susceptibility to fractures, as do smoking, lack of weight-bearing exercise, and a calcium-poor diet.
– A doctor might discuss the results of a test finding an inherited susceptibility to a form of breast cancer as, “You have a 45 per- cent chance of developing this form of cancer,” not “You will get cancer.”
-Which genes a cell uses at any given time depends upon environmental conditions both inside and outside the body.
-Like the Internet, a genome contains a wealth of information, but only some of it need be accessed.
– The use, or “expression,” of different subsets of genes to manufacture proteins drives the differentiation, or specialization, of distinctive cell types. An adipose cell is filled with fat, but not the contractile proteins of muscle cells. Both cell types, however, have complete genomes.
– Tissues intertwine and layer to form the organs of the body, which in turn connect into organ systems.
-Alleles are further distinguished by how many copies are necessary to affect the phenotype.
-A dominant allele has an effect when present in just one copy (on one chromosome), whereas a recessive allele must be present on both chromosomes of a pair to be expressed.
– The assumption is that the more similar the sequences are, the more recently two species diverged from a shared ancestor, and the more closely related they are. This is a more plausible explanation than two species having evolved similar or identical gene sequences coincidentally.
-Chimpanzees are more distinct from each other than we are!
-The most genetically diverse modern people are from Africa, where humanity arose.
-Forensic science is the collecting of physical evidence of a crime. Comparing DNA samples from evidence at crime scenes to samples from suspects often leads to convictions, and also to reversing convictions erroneously made using other forms of evidence.
-DNA profiling is useful in identifying victims of natural disasters, such as violent storms and earthquakes. In happier circumstances, DNA profiles maintained in databases assist adopted individuals in locating blood relatives and children of sperm donors in finding their biological fathers and half-siblings.
-Another use of DNA profiling is to analyze food, because foods were once organisms, which have species-specific DNA sequences. For example, analyzing DNA sequences revealed horsemeat in meatballs sold at a restaurant chain, cheap fish sold as gourmet varieties, and worms in cans of sardines.
-DNA analysis can clarify details of history. A famous case confirmed that Thomas Jefferson had children with his slave Sally Hemings.
-DNA testing can provide views into past epidemics of infectious diseases by detecting genes of the pathogens. For example, analysis of DNA in the mummy of the Egyptian king Tutankhamun revealed the presence of the microorganism that causes malaria. The child king likely died from complications of malaria following a leg fracture from weakened bones rather than from intricate murder plots, a kick from a horse, or fall from a chariot, as had been thought.
-Genes also affect how people respond to particular drugs. For example, inheriting certain gene variants can make a person’s body very slow at breaking down an anti-clotting drug, or extra sensitive to the drug. The person bleeds profusely at the same dose that most patients tolerate.
– Identifying individual drug reactions based on genetics is a growing field called phar- macogenetics
2)A second distinction of single-gene disorders is that tests can sometimes predict the risk of developing symptoms. This is possible because all cells harbor the mutation. A person with a family history of Huntington disease (HD; OMIM 143100), for example, can have a blood test that detects the mutation at any age, even though symptoms typically do not occur until early middle age, and the disease affects the brain, not the blood. Inheriting the HD mutation predicts illness with near certainty. For many conditions, predictive power is much lower.
3) A third feature of single-gene diseases is that they may be much more common in some populations than others. Genes do not like or dislike certain types of people; rather, mutations stay in certain populations because we have children with peo- ple like ourselves. While it might not seem politically correct to offer a “Jewish genetic disease” screen, it makes biological and economic sense—several disorders are much more common in this population.
4) A fourth characteristic of a genetic disease is that it may be “fixable” by altering the abnormal instructions.
-Tracking gene expression in cells can reveal new information about diseases. It can show that diseases with different symptoms actually share the same underlying genetic defect, or that conditions with similar symptoms have different causes at the molecular level.
-Metagenomics studies are showing how species interact, and may yield new drugs and reveal novel energy sources.
-Metagenomics researchers collect and sequence DNA, then consult databases of known genomes to imagine what the organisms might be like.
2)Nicholas’s digestive system was developing fistulas—holes that connect two parts that are normally separate. Food and feces leaked, and he became repeatedly infected. A feeding tube kept him from starving.
3)Nicholas’s pediatrician knew that the Medical College of Wisconsin had been planning an exome sequencing experiment
-4)Could they move it up to search the boy’s exome? The results might reveal mutations that could explain Nicholas’s symptoms.
5) The exome is the small part of the genome that encodes protein. Everyone’s exome has thousands of rare or even unique gene variants, and Nicholas’s has more than 16,000.
6)The paper described one of the genes found in the exome screen: XIAP. It had been known to affect the immune system, not digestion. But it does both.
7)The gene encodes a protein that normally keeps the immune system from attacking the intestines when it is fighting viruses. When the gene is mutant, fighting a viral infection kills intestinal cells, explaining Nicholas’s leaking digestive tract.
8) His version of the gene has a one-base difference from the healthy version. The gene is on the X chromosome, passed from carrier mothers to affected sons. The mutation was known to affect only one in a million boys, and no one had ever seen a boy with leaky intestines. 9)The known XIAP disease is lethal by age 10, but is curable with a bone marrow or stem cell transplant that would replace the immune system