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.
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 + or 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 are 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 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 negative fetus. If she is not given Rhogam within 72 hours after the birth of an Rh negative 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.
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.
The type of inheritance we have been discussing is called simple Mendelian inheritance and the traits we have discussed are controlled by genes at a single locus. Many traits are multifactorial. This means they are controlled by genes at several loci which are additive (polygenic) and other genes and the environment also play a role in the expression of the trait.
Examples of multifactorial traits include height, skin color, cleft lip and neural tube defects. If we use height as an example, we can say it is controlled by additive genes at four different loci. If you get all eight alleles for "tallness" you will be a one extreme of height, if you get eight alleles for "shortness" you will be at the other end of the height spectrum. If we lined everyone up according to height, they would fall into a bell-shaped curve with most being of medium height. Other factors influence height. There are genes on the X and Y chromosomes for height and people with extra X's or Y's are taller. Nutrition also plays a role. For example, you can see that second generation immigrants are taller than their parents if their parents came from a situation where they were not as well fed. Also, males are taller than females due to hormonal effects. Other genes can overcome the genes for height. For example, an achondroplasia gene will cause a person to be short independent of their genes for height.
Neural tube defects (NTD) such as anencephaly and spina bifida and also cleft lips are examples of multifactorial traits which show a threshold effect. This means you need a certain number of genes for NTD before the trait manifests itself in the phenotype. Folate, a vitamin, is an environmental agent which can affect the expression of the genes for NTDs. All of us carry some of these genes and depending on how many are carried by our partner and how many each gives to the sperm or egg, we may have affected children. If you are affected or a first degree relative is affected or if you have an affected child, you are at a higher risk than the general population risk for having an affected child because you probably have more of these genes.
Another type of human genetic disorder involves chromosome abnormalities. If the chromosomes do not separate as they should in meiosis, the egg or sperm can receive more or fewer chromosomes than they should. This condition is called aneuploidy which is caused by non disjunction of the chromosomes during meiosis (or mitosis). Fifty percent of first trimester spontaneous abortions are due to chromosome abnormalities. Animals do not tolerate deviation from the normal number of chromosomes. An extra chromosome is called trisomy and a missing one is called monosomy. There are no known autosomal monosomies.
In humans, the most common surviving chromosome abnormality is Down Syndrome (a.k.a. trisomy 21) which is due to an extra chromosome #21, the smallest chromosome (yes, it is smaller than #22). This causes the least imbalance but these children are not normal. They have a reduced IQ, are developmentally delayed, usually have heart defects and gastrointestinal defects, have a higher incidence of leukemia, are hypotonic (floppy babies), have a higher incidence of Alzheimer disease, and have an increased number of respiratory infections. Trisomy 13 and 18 are also known to survive to be born occasionally but usually die within a few months of birth.
The rate of non disjunction is correlated with maternal age. The probability of a woman having a fetus with a chromosome defect increases with age. At the age of 35 years, the risk of miscarriage due to a procedure called amniocentesis becomes less than the risk of having a child with a serious chromosome abnormality. The test is done usually between 15 and 20 weeks of gestation. So it is at the age of 34 or 35 that most women are offered this test which is virtually 100% accurate. A needle is inserted into the amniotic sac, and fluid is withdrawn which contains fetal cells. These cells are then karyotyped to detect aneuploidy. The fluid is also analyzed to detect NTDs or other abnormal openings in the fetus. While the test sounds scary or bizarre, it is done on a routine basis by obstetricians specializing in maternal fetal medicine and it is a safe test if done by an experienced practitioner. The State of California approves Prenatal Diagnostic Centers such as the one at King Drew Medical Center.
Because younger women have more children, they also have the most Down Syndrome babies (and other aneuploidies). Therefore, several years ago, the State of California implemented a simple blood screening called XMSAFP, (Expanded Maternal Serum Alphafetoprotein) done between 15 and 20 weeks gestation to detect aneuploidies and NTDs. Three different analytes in the mother's blood are measured and along with the age of the mother, a risk is determined by comparison with an extremely large sample of blood taken from women with normal and abnormal pregnancies. The data was collected by the Genetics Disease Branch over many years. This screening is only 66% accurate for Down Syndrome but is 99.9% accurate for NTDs. Ultrasound is another good prenatal test. It can tell accurately the gestational age, the number of fetuses, the location of the placenta and can detect many structural abnormalities.
Aneuploidy involving the X and Y chromosomes is more common in humans since the results are less devastating than autosomal aneuploidies. This is because the Y carries very few genes and, if you have more than one X, the rest are inactivated and only one is functioning in each cell. So women have only one functional X even though they have two X chromosomes. They are one kind of "genetic mosaic." At about the 100 cell stage or less, either the paternal X or the maternal X is turned off. Since it is random which one, the human female has some cells in which the paternal X is functional and the maternal X is not or vice versa.
The only known monosomy is monosomy X, it is also known as Turner Syndrome. Turner females are very short, and due to edema when a fetus, they have webbing of the neck and high arched finger and toe nails, they have non functioning ovaries and are therefore sterile, they may have horseshoe shaped kidneys and often have heart problems. Their behavior is somewhat unique and they tend to have spatial perception problems. The lost X is generally that of the father and so is not correlated with maternal age.
Klinefelter males are XXY. One of the two X's is inactivated. Klinefelter males are tall, sterile, have hypogonadism, have gynecomastia, broad hips and may have a slightly lower IQ compared to their normal sibs. Klinefelter and triple X are correlated with maternal age.
XXX, triple X females inactivate two of their X's. For the most part, they are normal and fertile but they are taller than their normal sisters, shy, and may be a little slow in school.
XYY males obviously arise from non disjunction in the sperm. They appear to be normal, are taller and may have a slightly reduced intelligence compared with their normal brothers.
The Y chromosome carries the gene for testis determination (TDF gene). In the developing embryo, the gonad and external genitalia are undifferentiated until about 7 - 8 weeks gestation. If the TDF gene is present, the gonads will go on to form testes, if not an ovary will form. Female is the default sex. There are several levels of sexual differentiation: chromosomal sex (XX or XY), gonadal sex (testes or ovary), internal plumbing sex (fallopian tubes, uterus or vas deferens, seminiferous tubules, epididymis), external plumbing sex (labia, clitoris or penis, scrotum) and psychosocial sex (which sex we feel we are). Most of the time we call the phenotype the external plumbing but that may not be consistent with the chromosomes or the gonads. There are several genetic disorders which result in ambiguous genitalia or in genitalia of one sex but gonads of the other. We also are beginning to gather evidence that homosexuality may in some cases be a genetically controlled trait.(You will have to take my course in human genetics to learn more).