Family pedigrees are used to illustrate inheritance of traits in families. Standard symbols are used such as a square for a male and a circle for a female. A short horizontal line between them indicates a mating. The male parent is usually placed on the left. A short vertical line is dropped from the center of the mating line and another horizontal line is drawn from which the offspring are indicated by dropping a short vertical line to a square or circle. Those individuals in the pedigree with the trait being studied are colored or darkened in. A legend indicates what the trait is. Each generation is indicated by a Roman numeral and each individual in a generation is indicated by an Arabic numeral. So each person is identified by two numbers, for example, II-3 or I-2, etc. Constructing pedigrees assists in analysis of modes of inheritance of traits.

Autosomal dominant (AD) and autosomal recessive (AR) traits are coded for by genes on the autosomes. Dominant traits require the presence of only one mutant gene for them to be expressed while recessive traits are those which require both alleles to be mutants. X linked recessive (XR) traits are those which have genes on the X chromosome. Males are affected if they have only one mutant gene since they only have one X. Females are less frequently affected since they have two X chromosomes and need mutant alleles on both for the trait to be expressed.

Examples of AR traits are albinism, sickle cell disease, galactosemia and phenylketonuria (PKU). The last three disorders are tested for in the new born screening in most states including California. To be a part of the new born screening panel, the trait must be common, the test relatively inexpensive and there must be a treatment for the disorder.

Galactosemia and PKU are enzyme deficiencies. Enzyme deficiency disorders are usually AR (homozygous) since a heterozygote, with one good allele, still makes enough enzyme to be healthy. This is a gene dosage effect. The one good gene will produce half the normal amount of enzyme. Since enzymes are very efficient, half is sufficient for normalcy. Babies with PKU or galactosemia are put on special diets to avoid the harmful effects of the enzyme deficiency. In the case of PKU, children are put on a diet low in an amino acid called phenylalanine. If they stay on the diet, they will avoid the otherwise inevitable mental retardation. Although adults used to be taken off the diet after their brain was fully developed, it was found that female PKU patients had severely mentally retarded children. The high levels of phenylalanine were toxic to the fetal brain development even thought the fetuses themselves did not have PKU (they are heterozygotes). It was also noticed that staying prevented slow loss of mental capacity that occurred off the diet.

Sickle cell disease is AR. The heterozygote carrier is said to have sickle cell trait. They are usually symptom free. The frequency of carriers among African Americans is 1/10 to 1/12. This relatively high frequency is due to a phenomenon known as heterozygote selection. In regions of Africa where the malaria parasite was prevalent, the heterozygous state proved to be advantageous. The malaria parasite did not like the abnormal hemoglobin made by the sickle cell gene and did not infect the heterozygote. Therefore the heterozygotes survived while the homozygous normal individuals died of malaria and the homozygous mutant died of sickle cell disease. Today the carrier frequency remains high and all African Americans may want to be tested to see if they are carriers. If two carriers have children, 25% of the offspring will have sickle cell disease which is a very debilitating disorder and one which reduces life expectancy. Babies that screen positive for the disorder in the new born screen, are put on penicillin prophylaxis as a treatment. Sickle cell disease is harmful to almost every organ system of the body. This is said to be a pleiotropic effect. The name, sickle cell, came from the fact that at low oxygen tension (e.g., at high altitudes) the red blood cells take on a sickled shape because of the way the mutant hemoglobin molecules interact. These sickled cells can get blocked in the blood vessels causing a variety of problems including great pain.

Achondroplasia, a short limbed dwarfism, is a relatively common AD disorder. Older fathers are the source of new mutations that cause achondroplasia. An achondroplastic dwarf can expect that half of her/his children will have the trait. Only recently was it known that a double dose of the gene for achondroplasia is lethal. There is a support group for people with short stature called Little People of America. People of short stature often marry others like themselves. It was found that when two achondroplastic dwarfs marry, 25% of the fetuses die. So it is not a "true" dominant since the person who is a heterozygote with one copy of the gene is not the same as a homozygote with two copies of the mutant gene.

Many AD traits show incomplete penetrance and variable expressivity. An example is polydactyly. People with the gene may have extra fingers on one, both or neither hand and the same is true for the toes. So people in the same family with obviously the same genotype may not express the same phenotype. This is called variable expressivity. And sometimes an individual, in the same family, who has no extra digits, will have children with extra digits. In this individual, the gene is said to be incompletely penetrant.

Osteogenesis Imperfecta, known as brittle bones, is another AD disorder and is due to mutations in the genes for collagen. It can be inherited but often it is due to new mutations. In one case a man had two children with OI by two different women. He was not affected. An analysis of the DNA from his sperm showed a significant proportion carried the mutant gene. The mutation had probably occurred in a "feeder cell" in his testis which gave rise by mitosis to a significant population of primary spermatocytes.

Progeria is an AD disorder which causes premature aging. It is never transmitted from parent to child since the individuals with progeria do not live long enough to reproduce. A disorder of this type is referred to as a genetic lethal. All new cases are due to new mutations.

X linked traits are those whose genes are on the X chromosome. Although the X is called a sex chromosome, it has only a few genes that are involved in sex determination. There are hundreds of genes on the X, many of which have been mapped, and the vast majority have nothing to do with sex. Relatively common XR traits are color blindness and hemophilia. XR traits are much less common in females than in males due to the presence of the second X in the female. If one in ten men is color blind, one in one hundred females is color blind. All the female offspring of a color blind man will be carriers. If a color blind male married a female carrier, then half their daughters will be color blind. The hemophilia gene carried by Queen Victoria was widespread among European royalty. One interesting family was the Russian Royal family who had a son with hemophilia. They allowed themselves to be politically manipulated by a person who claimed to be able to help the boy. The result helped trigger the Russian Revolution in 1917.

There have been other examples where genetics has played a role in politics. In Russia, the general opinion was that environment was the primary determinant of the individual whether that is a person or plant. They believed in the inheritance of acquired characteristics. So the Russians decided to grow wheat in extremely cold regions but failed because they failed to first find wheat that was genetically different and capable of growing in the cold climate. They found that the wheat did not adapt and that they could not force the regular wheat to grow in a climate to which they were not adapted. The result was a major catastrophe and they ended up, much to their chagrin, having to buy wheat from the United States. Genetics only later found its way into Russian science. Another example of the misuse of genetics was the fascist movement of Adolph Hitler. He along with others made the decision that certain groups of people were superior and others were inferior. He eliminated the physically and mentally disabled and gypsies in addition to the six million Jews he sent to concentration camps to be murdered. This is sometimes referred to as eugenics. When people decide who is superior, it is no accident that those who are said to be superior also happen to be like the ones making the decision. Later in the semester we will have a lecture by survivors of Hitler's holocaust.
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