{The Human Genome

The way to get started is to quit talking and begin doing

-Walt Disney

A human karyotype – A picture of chromosomes arranged, by pairs, in order from large to small. Is this person a boy or girl?

A pedigree chart shows how a trait is passed on from one generation to the next.

Human Blood type. A person with type A blood has antigen A as part of their Red Blood Cells. They also have antibody B in the plasma of their blood. So, if a person with type A blood receives type B blood the antibody B in their plasma will attack the B antigen on the donated RBC’s and the cells will clump up and the recipient may die.

Why is type O- considered the universal donor?Why is AB+ considered the universal recipient?

Karl Landsteiner disovered the blood groups in 1901. The first successful transfusion was in 1907. The ability to transfuse blood saved many lives in WWI

The Rh factor is determined by a single gene with two alleles. The Rh+ allele is dominant over the Rh- allele

Recessive Autosomal genetic disorders;Cystic Fibrosis – 1/2500 Caucasian babiesPhenylketonuria (PKU) – 1/10,000 births in the US

Dominant Genetic DisordersHuntington's disease (HD) is a neurodegenerative, genetic disorder that affects muscle coordination and leads to cognitive decline and psychiatric problems. It typically becomes noticeable in mid-adult life.

Abnormal genes give researchers clues about the normal fumction of the gene.I.e. PKU is caused by one missing enzyme which leads to the inability to metabolize the amino acid phenylalanine.

Cystic Fibrosis (CF) is an autosomal recessive genetic disorder.It is caused by a mutation in the gene for a protein that regulates chloride and sodium ions and results in thick, viscous mucus in the lungs and body.

Panel 1 shows the normal channel protein that controls the flow of HOH and Cl- ions into and out of the cells in the lungs.Panel 2 shows the defective protein, blocking the flow and causing CF.

Ventilators, antibiotics, nasal operations, digestive operations, and inhalers are used to help CF patients stay healthy. Lung transplantation often becomes necessary.

Sickle cell anemia is caused by a mutation of single nucleotide in one of the proteins that makes up RBC’s. It causes these cells to become bent and rigid. This results in clogged capillaries and eventual organ death.

Sickle cell anemia is a recessive genetic disorder. If a person is homozygous for the gene they develop the disease.If a person is heterozygous they may develop symptoms if under oxygen stress.

People who are heterozygous for Sickle cell anemia (Ss) are much more resitant to malaria. The RBC’s rupture before the malarial plasmodium has time to mature. This may be why the disease persists. The map shows the distribution of sickle-cell trait. This closely matches the incidence of malaria in these regions.

Because it is small chromosome 22 was sequenced first (1999). It has 49 million DNA base pairs (A – T etc.). This represents about 693 genes. It has long stretches of repetitive DNA that does not seem to code for proteins.

Originally thought to be larger, chromosome 21 was sequenced in 2000. It contains the gene that causes amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease.

ALS is an autosomal dominant genetic defect. It causes degeneration of the upper and lower motor neurons. Unable to function, the muscles of the arms, legs, breathing, swallowing and talking eventually weaken and disappear. Once diagnosed patients usually do not survive for more than 5 years.

Lou Gehrig farewell, July 4, 1939, 61,000 people at Yankee stadium. First number to be retired. He would be dead in 2 years

Because the Y chromosome is much smaller than the X there are situations where a gene is located on the X chromosome but does not have a corresponding site on the Y. These genes are said to be sex-linked.

Color Blindness can be passed on by a mother who carries this recessive gene. How could a girl be color blind?What are the odds of a boy being color blind in this situation?

One of the X chromosomes in female mammals is inactivated. This prevents the female from having twice as many X chromosome products as the male. Once the X chromosome is inactivated it will remain that way. This was first discovered in Cats.

The inactive X chromosome forms a discrete body in the nucleus called a Barr Body. In the top photo Xa is the active X chromosome and Xi is the inactive X chromosome. The bottom photo shows the presence of the Barr body in the nucleus of a cat egg cell.

Non-disjunction is the failure of chromosomes to separate properly during mieosis 1 or 2. This results in one cell having one more chromosome and the other having one less.

Down’s syndrome is the presence of an extra chromosome #21 (trisomy). This results in many physical and mental problems for the poor person afflicted.

Turners syndrome is the presence of only one X chromosome (monosomy X) for the female. Since the ovaries and uterus do not fully develop these people are sterile

The restriction enzymes always cut the DNA through the same base pair. (i.e. A – T). This breaks the DNA into pieces. The pieces move at different rates through a gel according to their size. Since everyone’s DNA is unique the pattern of bands is unique as well.

First developed in the 1980’s DNA fingerprinting has been invaluable in finding criminals and setting unjustly accused people free.

The Human Genome project is a collaborative effort to identify and map all of the genes of the human genome.

By using widely separated bits of bases as markers researchers are able to sequence DNA bases faster.

Shotgun sequencing is breaking DNA into random fragments, sequencing the fragments and then reassembling the fragments on the basis of the overlapping regions.

Gene therapy is the use of DNA as a way to treat a disease. The most common method is to replace a faulty gene with a normal one.

Researchers find genes by looking for promoters. Promoters are sequences of bases on DNA that are sites for RNA polymerase to attach to. They are always just ahead of a particular gene.