Biology 102 - General Biology

Human Genetics

Human Mendelian Inheritance

Humans have 46 chromosomes in every cell in their bodies, 23 from their mother and 23 from their father. However we have 24 different chromosomes or linkage groups. Genes on the same chromosome are said to belong to a common linkage group. We have two chromosomes, the X and the Y which are the sex determining chromosomes and are therefore called the sex chromosomes. However, the X and Y chromosomes have genes for traits other than sex. The genes on the X form one linkage group and the genes on the Y form another linkage group. The other 22 pairs of chromosomes are called autosomes. The genes on chromosome one form one linkage group, the genes on chromosome two form another linkage group, etc. So there are 22 autosome linkage groups plus the X and Y linkage groups to give you a total of 24 linkage groups.

There are some common misconceptions about the term genetic that should be corrected. Genetic does not mean unchangeable. For example, hair color is genetic but one can dye ones hair. Also, children born with inborn errors of metabolism can be put on special diets to correct their genetic disorder. The genotype cannot be changed but the phenotype may be changed.

The term, congenital, refers to conditions with which one is born. Some congenital defects are genetic and some are not. Some congenital disorders can be due to teratogens (environmental agents which cause the embryo to develop incorrectly). Also there are genetic conditions such as Huntington disease (which causes dementia and involuntary movements) which has an onset later in life, usually in the forties or fifties. This condition is not congenital but it is genetic. Therefore, not all congenital disorders are genetic and not all genetic disorders are congenital.

Some people confuse dominant traits with prevalent. Dominant refers to a pattern of inheritance of a trait and not the proportion of people with the trait. Also, people with dominant traits do not pass the trait onto all of their children. They are usually heterozygous and only 50% of their children would be expected to be affected. Sometimes people who inherit the gene for a dominant trait may not express it. This is known as incomplete penetrance. Polydactyly (extra fingers and/or toes) is an autosomal dominant trait. Only 50% of the children of a person with polydactyly would be expected to be affected. However, some people inherit the gene but never express it phenotypically. They may pass the gene to a child who does express the polydactyly phenotype. Also dominant traits often show variable expressivity. This means the extent to which people with the same genotype can vary. For example, in the same family some people with the gene for polydactyly may have extra fingers on none, one or both hands and/or extra toes on none, one or both feet or some combination of these possibilities.

Only sex-linked or X-linked recessive traits "skip generations." That is because genes on the X chromosome are expressed in the male but usually not in the female since she has another X which will usually have the normal allele. X-linked traits are passed by the mother to 50% of her sons. 50% of her daughters will be carriers who can also pass the gene to their sons.

Traits can be genetic without having a simple all or none effect. Eye and hair color and height are examples of genetic traits which involve many pairs of genes. These traits are called multifactorial to describe the fact that several gene pairs are involved along with environmental influences in their expression.

Blood Groups: ABO and Rh

Usually you are given your blood type as "A+" or "O-" etc. The letter refers to the ABO blood type and the + or - refers to the Rh (Rhesus) blood type. Humans have many other blood types but these are the most medically important.

In the ABO system there are three alleles in the population, A, B and O. The A allele makes an A antigen on the surface of the rbc, the B allele makes an antigen on the surface of the rbc and the O allele makes no antigen. A and B are codominant. Both alleles make antigens when present in the same individual. A and B are both dominant to O. If a person's phenotype is type AB, you know their genotype is AB. If a person is type O, you know their genotype is OO. But if a person is type A, they can be AA or AO. And if a person is type B, they could be BB or BO. Only if you know more about their parents' or children's blood types could you possibly know their genotype.

Unlike the Rh system, people have preformed antibodies to the A or B antigens they do not have on their rbcs. Thus, a person who is type A has antibodies to B and a type B person has antibodies to A, a type O person makes antibodies to both A and B, and type AB people do not make antibodies to either A or B antigen or they would destroy their own rbcs. Type O is the universal donor and type AB is the universal receiver. Generally, blood typing occurs before you are transfused and you are given an exact match for both ABO and Rh blood types. (Sometimes transfusions do not include the blood cells and there would be no compatibility problems.)

Before the days of DNA fingerprinting, ABO blood types were used as evidence in paternity testing or forensic tests. For example, a putative father who is type O could be ruled out as the father of a type AB baby or a type AB man could not be the father of a type O baby. But type AB is very rare so in most cases a man could not be ruled out, he could only be said to be a possible father. In other words, a person with a rare blood type might be ruled out if they were not guilty but proving a person was the culprit was difficult since all of the blood types are rather frequent. DNA testing now allows the testing of many different genes at many different loci the probability of detecting identity has reached a high degree of sophistication and probability.

Although the Rh blood typing system is really more complex than described in our text, we generally simplify it and say there are two alleles, Rh+ and Rh- in the population. And each person has two alleles and can be homozygous Rh+, heterozygous or homozygous Rh-. The Rh+ allele makes a cell surface antigen that appears on the red blood cells (rbcs) and the Rh- allele does not make this antigen. Therefore, Rh+ is dominant to Rh-. If you are Rh positive, you could be homozygous or heterozygous (+ + or + -). If you are Rh negative, you have to be homozygous recessive (- -).

An important medical fact is that if you are Rh negative you should never be given Rh positive blood or you will be "sensitized" and make antibodies to the Rh factor (antigen). A second transfusion of Rh+ blood could cause you to go into anaphylactic shock and die. Women who are Rh negative and who have a child who is Rh positive (the child would be heterozygous, incidentally) may not have a problem with the first Rh+ pregnancy because fetal blood does not mix with the mothers blood and she cannot become sensitized. However, at birth when the placenta is removed, some fetal blood leaks into the mother's circulation. Her immune system "sees" the Rh antigens on the fetal cells in her circulation and she begins to make antibodies to them. If she is given Rhogam (Rh gamma globulin) within the first 72 hours of birth, she will not be sensitized.

Rhogam is prepared from the gamma globulin fraction of blood of Rh- people who have been exposed to the Rh+ antigen and who have made antibodies to it. The Rhogam acts as a passive immunization. The Rh antibodies in the Rhogam will clump and destroy the fetal blood cells with the Rh antigen on them. If they are thus removed from the maternal circulation, her immune system never sees the antigen and she is not sensitized since her immune system did not "see" the Rh antigen and did not make antibodies to it. Rhogam thus protects subsequent Rh positive pregnancies but must be given each time the woman is pregnant with an Rh positive fetus. If she is not given Rhogam within 72 hours after the birth of an Rh positive baby, she will begin to make antibodies to the fetal blood cells. In a subsequent Rh+ pregnancy these antibodies can pass across the placenta to the fetus and destroy the fetal red blood cells. This causes a serious, if not lethal, condition known as erythroblastosis fetalis. After a spontaneous, elective or therapeutic abortion or an amniocentesis, an Rh negative woman should be given Rhogam as a precaution.

Pedigrees are Necessary

How to construct your family pedigree

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.

Genetic counseling is a relatively new profession and there are master's degree programs designed to train individuals for this career. In California there are two programs, one is at CSUN and one is at UCI. Genetic counselors work with prenatal, pediatric, and adult patients referred from a variety of clinics such as neurology, infertility, ophthalmology, endocrinology, dermatology, cardiology with genetic disorders. In addition to the medical records, the genetic counselor relies heavily on family histories and records the pedigree of each patient. The genetic counselor not only knows a lot about the genetic disorders but is also skilled in communicating information about the disorder, its inheritance pattern, and the risks of recurrence in an understandable way to the person who has come for testing or who has been diagnosed with a genetic condition.

Patterns of Inheritance

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.

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.




CLINODACTYLY (curved little finger)

Can be of fingers or toes or both


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.



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.



Can be of both skin (cutaneous) and eyes (ocular)
Occurs in all organisms and in all races of humans

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. Babies with galactosemia are taken off regular milk since it contains lactose (milk sugar) which they cannot metabolize. They receive a milk substitute. 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 though 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.

This recessive disorder has a higher incidence in Africans because the gene protected against malaria

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.


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 determination. 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.


Duchenne Muscular Dystrophy (DMD) is an X-linked recessive trait. The gene for DMD is carried on the X chromosome. Women who carry the gene are heterozygous (they have two X's) and they are not affected. However, 50% of the sons of a carrier female will be affected since they have only one X chromosome. Fifty percent of a carrier's daughters will be carriers. Females are not affected since they would have to have a mutant gene on each of their X chromosomes. They would have to have a carrier mother and an affected father but males affected with DMD do not live long enough to reproduce.


Hunter syndrome is an X-linked disorder. It is one of a group of disorders known as lysosomal storage diseases caused by the loss of one of the lysosomal enzymes. The lost enzyme in Hunter syndrome degrades an extracellular protein called a mucopolysaccharide. The substrates that cannot be degraded accumulate in the lysosome. This eventually causes the death of the cells. Hunter syndrome is due to the loss of a lysosonal enzyme coded for by a gene on the X chromosome. Like DMD, only males are affected. Since affected males do not live long enough to reproduce, no females are affected. The other lysosomal enzyme disorders are coded for by genes on autosomes and are inherited in an autosomal recessive pattern. Tay-Sachs Disease is an AR lysosomal storage disease found primarily in Ashkenazi Jews.


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.