II. Local polymorphisms.

III. Local disorders.

Terms

Note Page 425: The definitions of polymorphism are somewhat off target. A locus is polymorphic if two or more alleles have frequencies greater than 1%. It is true that this is greater than can be maintained by mutation, but that is not part of the definition.

I. Many loci are polymorphic world-wide. Ca. 50% of the genes that code for enzymes are polymorphic, with somewhat lower frequencies for genes whose products have other functions. Among the best studied of the world-wide polymorphic genes are the following:

A. The ABO blood group locus was the first human polymorphic system to be recognized.
1. Because of that, because other polymorphic systems were slow to be identified, and because of the clinical importance of the ABO groups in blood transfusions, this locus has been studied in more populations than any other locus.

2. O is the most common allele in most populations. A occurs in most populations and is quite high in some, the major exception being Central and South American Indians, in whom it is absent. (But there is a center of high A frequency in Western Canada.) The B allele is highest in Asia but is absent in the closely-related Amerinds.

B. The Rh blood groups are another universal polymorphism.
1. The highest frequency of the Rh– (r) allele is in the Basques, who are thought to be a remnant of the ancient people who occupied Europe. The lowest frequencies of r are found in Southeast Asian populations.

2. The R^o allele (one of several alleles that comprise the Rh-positive "allele") is found primarily among persons of African ancestry. Other major Rh+ alleles are found in all populations, although the frequencies vary.

C. The MNSs blood groups are another example of world-wide polymorphism. This system consists of two closely-linked loci that code for common red cell surface receptors, glycophorins A and B. Each locus has two common alleles, making four haplotype combinations (MS, Ms, NS, Ns), all of which are found in virtually every human population.

D. Lactase persistence is a dominant trait that varies from very high frequencies in Scandinavian countries to very low frequencies in Asia. Lactose is the sugar in milk. Lactase is an enzyme required to break it down. In most mammals, production of lactase in the intestinal tract ceases after the usual period of nursing. This is also true of most humans. After that time, the lactose in fresh milk cannot be broken down properly, and the bacteria in the gut have a great time with it, causing great discomfort to the host. If a person is either homozygous or heterozygous for persistent lactase, there is no problem. There are now various processed milks and things to add to whole milk to remove lactose for the benefit of persons who lack lactase.

A. The Fy^o allele of the Duffy blood group system occurs in ca. 100% of sub-Saharan Africans and is rare in other populations. The Fy locus is the red cell surface receptor for vivax malaria. Non-African populations are polymorphic for two alleles, Fy^a and Fy^b. Persons with any combination of these two alleles are susceptible to vivax malaria. Africans and African-Americans who are homozygous for Fy^o are not susceptible to vivax malaria.

B. The Di^a allele of the Diego blood group system is found only in Asians and Amerinds and supports the close genetic affinity of these populations.

C. Sickle-cell anemia occurs primarily among persons of African ancestry. It also occurs in a few groups in the Mediterranean area, as well as in small groups in the Arabian Peninsula and India. The Hb S allele occurs at very low frequencies if at all in other populations. Other Hb mutations, such as Hb E and thalassemia mutations do occur in polymorphic frequencies in some of these other populations.

D. G6PD deficiency (glucose 6-phosphate dehydrogenase, an enzyme that helps metabolize the sugar glucose) occurs primarily in persons of African ancestry. It is an X-linked recessive trait, with occasional expression in heterozygous females. The deficiency has no effect on the phenotype unless the person is exposed to certain drugs, in which case it can cause destruction of red blood cells. Other alleles of the G6PD locus are polymorphic in some other populations. Of particular note is an allele that occurs primarily in Italy and the Eastern Mediterranean that causes males to be very sensitive to fava beans.

A. Tay-Sachs disease is rare except among Ashkenazic Jews. (Ashkenazic Jews are those from Eastern Europe and include most Jews in the U.S.)

B. Cystic fibrosis is rare except among persons of European ancestry.

C. Congenital dislocation of the hip occurs with very high frequency among the Navaho. The cause is unknown, but the disorder is probably a complex inherited trait.

D. Diabetes mellitus type 2 occurs with high frequency among certain Indian groups, e.g. the Alabama-Coushatta in East Texas and especially the Pima Indians of Arizona.

E. U.S. Blacks have a high frequency of hypertension and heart disease of unknown cause. It is thought by most to be inherited.

F. The high risk of breast cancer in some families is associated with inheritance of mutations at either the BRCA1 or BRCA2 locus. Many different mutations have been found at these loci. Most are individually rare. However, several occur at high levels in certain populations.

1. The BRCA1 mutation 185delAG occurs in ca. 1% of Ashkenazic Jews. Women who inherit this mutation have a high risk of developing breast and/or ovarian cancer. Among Jewish women who have breast cancer, 20% inherited this mutation.

2. The BRCA2 mutation 6174delT is found in 8% of Ashkenazic Jewish women who have breast cancer.

3. BRCA2 mutations also carry a risk of breast cancer in males. In Iceland, 40% of males with breast cancer inherited a 5 bp deletion in BRCA2. This particular mutation, but not others, occurs with high frequency in Iceland.

Back To:
ZOO 317 / Course info / Lecture sched / Last lecture / Next lecture / On-line resources