A Tutorial in Basic Genetics

by Lynne Gildensoph, PhD (Associate Professor of Biology, the College of St. Catherine, St. Paul, MN)

Introduction

This basic tutorial is meant for those who are contemplating Assisted Reproductive Technology (ART), potentially using donor eggs and/or sperm.  Although it appears possible to pick the traits of your child, it is not really so easy, as nature intended populations of organisms to exhibit wide variation in traits.  Thus, sexual reproduction, the process that evolved to produce offspring, incorporates procedures that ensure genetic diversity.  In addition, the environment an organism encounters also plays a role in how those traits are expressed.  Hopefully this basic lesson in genetics will help you understand how difficult it is to choose your child’s traits – even when the outward traits of the parents are known.

Variety is Essential

Evolution is the process whereby all species on earth come to occupy particular niches where their characteristics best suit them. When an environment changes, then those organisms which have previously existing mutations in the DNA for particular traits will survive and pass those traits along to their offspring (this is called fitness in an evolutionary sense) who then become the basis for a new population.  Thus, genetic diversity is critical to the survival of any population, especially in the face of a dynamic environment.

How do organisms ensure that genetic diversity exists?  Sexual reproduction is critical.  The keys to genetic diversity lie in two processes: one, called meiosis, is a special form of cell division that produces the gametes (eggs and sperm), and the other is fertilization, where the gametes of two unique individuals come together to form a new cell (the zygote), which will ultimately form the embryo – which develops into the new individual.  This new individual is genetically distinct from its parents – and will have traits from each of them.  Although it is impossible to predict which traits will be expressed, for humans, genetic testing exists to determine if genes for familial diseases (such as cystic fibrosis) have been passed from parents to child. This testing may take place pre-implantation (on an embryo created via in vitro fertilization in the lab), or post-implantation by removing fetal cells from amniotic fluid (amniocentesis) or through removal of a small piece of the fetal portion of the placenta (chorionic villus sampling). These testing protocols are available for a variety of inherited diseases, but not for what are termed cosmetic traits, and take place under the direction of expert health care personnel, such as a physician or genetic counselor.

Adult humans typically have 46 chromosomes in the nucleus of each cell, except for the sperm and eggs, which have half the typical number.  These chromosomes, which carry the DNA coding for all traits in that person, exist as 23 pairs.  One of each pair came from the mother and one of each pair was inherited from the father.  Thus, each person has genes (pieces of DNA that code for particular proteins) from both parents. These proteins control a person’s traits– from the way they look to their internal biochemistry). But, the story isn’t that simple, because during the process of meiosis the genes from these parents get mixed up – so that each gamete is a unique mix of genes from that person’s parents, and the environment is also important in the expression of those genes.

Meiosis

Meiosis is a process that occurs only in specialized tissue.  In males, this process takes place in the testes, and the ovaries serve this function in females.  During meiosis, the total number of chromosomes is split in half, so that each gamete typically only has 23 chromosomes (one of each pair). When one egg and one sperm join during fertilization, the typical human chromosome number, 46, is restored – and the new individual has 23 pairs of chromosomes, one of each pair from each parent.

A couple of very interesting things take place during meiosis.  Each pair of chromosomes sticks together, and they exchange pieces of DNA in a process called crossing over. So now, the chromosome from the mother could have some pieces of DNA from the chromosome from the father, and vice-versa. This is the first event that generates genetic diversity. These stuck-together chromosome pairs then line up in the middle of the cell – and each pair has a 50/50 chance that the chromosome from the mother or father will be on the “north” or “south” side of the cell, since each of the 23 pairs lines up independently of each other pair. This process is called independent assortment. The chromosome pairs are then split apart, so that the resulting eggs or sperm will have only one of each pair (23 chromosomes), as discussed above and the mix of chromosomes from either parent is random.  Thus, the gametes will have unique combinations of genes from this parent – as both crossing over and independent assortment ensure genetic diversity in the gametes.

Fertilization

During sexual reproduction the gametes will meet and fuse, and the new zygote, or first cell that results from this fusion, will have 46 chromosomes, restoring the typical number of chromosomes found in humans. This happens when sperm attach to the outer surface of the egg – and one sperm digests the outer coating of the egg, allowing the nucleus of the sperm to move into the egg cell.  These nuclei then join, creating the nucleus of that first cell – the zygote.  This cell then divides by conventional means (mitosis) to produce a multicelled embryo, which, once implanted into the inner layer (the endometrium) of the uterus, will continue to divide and differentiate into the fetus, which will ultimately be born as a baby.

Gene Expression

Humans have about 30,000 genes, and these genes contain the instructions for all of the proteins that will be made by that person’s cells over the course of their lifetime.  These genes are turned on and off by various biochemical signals, and generally, cells make proteins only as needed for growth and development and for metabolism.  Although some traits are controlled by simple dominant and recessive genes, this is not true for many traits.  An example of a trait that is controlled by simple dominance is thumb folding.  Clasp your hands together and interweave your fingers.  Which thumb is on top? Some people clasp their hands with their left thumbs up, and others have their right thumbs up.  Try to reclasp with the other thumb in that top position – it feels kind of uncomfortable, right?  This trait is controlled by one pair of genes – and whether you clasp with your left or right thumb on top is determined by that one pair of genes you inherited from your parents.  If you inherited one dominant gene and one recessive gene from your parents (Tt), then you will express the dominant trait (left thumb on top).  You may have inherited two copies of the dominant gene (TT), one from each parent, which means that you will express the dominant trait.  But, if you inherited two recessive copies of the gene (tt), then you will clasp hands with the right thumb on top.  These different forms of a gene, for example this gene for thumb folding, are called alleles. The dominant allele is generally denoted with a capital letter and the recessive with a lower case letter. Each person typically has two alleles for each trait (one on each of the pair of chromosomes that carries the gene for that particular trait.)

Most traits, however, are controlled by much more complex systems, and even those that are inherited as simple dominant/recessive pairs are more complex than what is shown above. For a good number of traits more than two alleles exist in the population, and some traits are coded for by genes that are co-dominant with each other. For example, human blood types are coded for by three different alleles, and two of the alleles (A and B) are co-dominant.  Thus, if you have Type A blood, you can either be AA or AO.  People with type B blood are either BB or BO.  But, if you inherit one allele for A and one for B, then your blood type is AB.  Those who inherit two recessive alleles for blood type are OO.

In addition, some traits are controlled by more than one pair of genes (polygenic inheritance or multifactorial inheritance).  This is true for height and skin, hair and eye color.  The number of dominant or recessive alleles a person inherits will control these traits. Let’s say, for example, that height is controlled by three pairs of genes (6 alleles) on three separate chromosomes.  Because of the random mix of genes that results from meiosis (crossing over and independent assortment) and fertilization, a person who inherits three of the six alleles as dominant would be medium height. A person who gets six dominant alleles would be tall and those with all six of those genes in recessive form would be short.

And, because traits are expressed in very complex ways, with signals to turn genes on and off and intricate pathways, the biochemical environment the cells live in is also an important factor. This can be impacted in various ways – for example, through nutrition. For some pathways it is necessary to have a particular vitamin or mineral as a co-factor in the biochemical reaction. If this is not readily available, the pathway may not function as it should – resulting in a variation in the trait that was inherited.

Some traits are sex-linked, which means they are carried on the X chromosome.  Since females typically are XX, and males are typically XY, males who inherit a mutated form of a gene will express that trait, since there is not another X chromosome with a potentially different allele for that trait to compensate.  This is the case with a number of inherited diseases – such as hemophilia and Duchenne muscular dystrophy.  Females, who have two genes for these traits, are much less likely to express these diseases – although they may be carriers.  For example, a woman who is a carrier for the recessive trait hemophilia would carry alleles that are XCXc. If she has children with a man who does not have hemophilia (XCY), then one half of their boys have the potential for this disease, and one half of their girls are potential carriers.  They may, of course, never produce a son with hemophilia – it is random chance that an egg with Xc will fuse with a Y-bearing sperm.

Conclusion

The inheritance of alleles is a somewhat random process and “nature” interacts with “nurture” in such a way that both the alleles and the environment in which those genes are turned off and on are important to the development of particular traits in an individual.  This tutorial is only meant to give you a small taste of the complexity that is inheritance.  If you would like more information about the processes described above, a good Biology textbook for high school or college biology classes would help.  A good web source of information is the National Institutes of Science Handbook http://ghr.nlm.nih.gov/handbook  from the NIH Genetics Home Page http://ghr.nlm.nih.gov/