Sperm and egg unite; it is the symbiosis of a new life, the beginning of a new being. Paternal and maternal progenitor beings have each contributed a blueprint containing one half of their own genetic recipe. In the case of humans, 23 chromosomes each will merge to form the offspring’s inventory of 46 DNA molecules. Well, in most cases that is. The classic allotment of chromosomes is referred to by endocrinologists and geneticists as a karyotype.
Perhaps the most obvious facet of inheritance is that expressed through chromosome pair 23. There are actually two flavors of this chromosome and they are labeled X and Y. A normal female karyotype is referred to as 45XX and a normal male karyotype as 45XY. Sperm cells are formed in the male testicles through a process known as meiosis. In this process, a special type of stem cell is divided in half. The resulting sperm cells each contain 23 chromosomes, and half of those will exhibit an X chromosome and the other half a Y chromosome. Meiosis in males is a process which can continue throughout life, but in females it takes place only once when the woman’s ovaries are formed. In the feminine case, an allotment of about 400 immature eggs is produced by meiosis, and each will carry only one X chromosome.
In the case of Chromosome pair 23, the Y chromosome is always dominant, and when present always results in an offspring of predominantly male gender. There are exceptions however. One of the most interesting of these is a condition known as Turner’s syndrome. In this case, the daughter ( this condition only occurs in the female gender) may have a karyotype of 45XO (a totally missing sex chromosome) or 45XX with one good X Chromosome and one deformed one. In many cases, Turners syndrome is inherited from one of the parents, but can also result through polymorphism during DNA molecule replication as part of a process known as cellular mitosis during the embryonic phase of development. Since each parent provides one X chromosome to the offspring, Turner syndrome can be inherited from either progenitor.
In another case involving Chromosome 15, an unusual inheritance pattern was discovered in the 1980’s. This condition actually involves a missing chunk of the DNA molecule. Again, the condition can be inherited from either parent, but the amazing thing researchers learned about this genetic anomaly was, that dependent on which parent the defective chromosome was inherited from, a different syndrome would result. Prader-Willi syndrome is the resulting manifestation when the paternal chromosome 15 is effected and Angleman’s syndrome is the result when the maternal chromosome 15 carries the anomalous allele.
Naturalist studying inheritance traits in the 19th century saw that anomalous conditions observed in parents or grandparents would often show up in children or grandchildren. Gregor Mendel was one such naturalist who experimented with pea plants to understand the patterns of inheritance. His work which was quite remarkable, would go unnoticed until early in the 20th century when it was hailed as profoundly astute. Even before scientists knew anything about the DNA which carried the traits of inheritance, they began to recognize certain consistent patterns of genetic expression, and these patterns are fraught with complexities. For instance, the chances that a male grandchild will have the exact same 23 chromosomes as one or the other of its grandfathers is about 1 in 833,608. But this is just a statistical prediction and there are less complex instances where simpler patterns of heredity are apparent.
DOMINANT AND RECESSIVE ALLELES
Genes are basically specific DNA sequences that code for proteins. Humans have about 30,000 active genes represented by about 1 percent of the nucleotides in our DNA. The rest of our DNA is made of telomeres and junk, nucleotides that may once have coded for proteins (active genes), but which have become defective or obsolete. It’s a process called variation through instances of genetic polymorphism, or more simply put, evolution.
Which chromosome and where on that chromosome a gene is located, is referred to as its locus. Not all genes are created equal, some code for slightly different variations of proteins and some genes are broken in that they have been miscopied at some point and don’t code for a valid protein. Variants of genes or a different version of a specific gene are referred to as alleles. Basically, we receive two alleles for each gene, one from each parent.
In 1865, based on his breeding experiments with pea plants, Gregor Mendel defined two laws of heredity, the Law of Segregation (1st Law) and the Law of Independent Assortment (2nd Law). For a century, these laws seemed to be pretty concrete, but as we have learned more about DNA and genes in the past 30-40 years, we know that Mendel’s laws only hold true in cases where a single gene controls a specific inherited facet. Nevertheless, Mendel’s laws are expressed as instances of dominant and recessive genes, the notion that one allele takes precedent over another. In reality, it doesn’t really work that way, although on the surface of it may appear to.
For instance, red hair is a recessive trait associated with a protein called MC1R that suppresses production of red pigment. If you receive a broken MC1R allele from one parent and a good one from the other parent, the good one is always dominant. If however, you receive two broken alleles for the gene that codes for MC1R you will lack the red pigment suppressing protein and thus end up with red hair.
Eye color is another attribute which generally follows Mendel’s law of dominant and recessive traits, although, today we know that there are multiple genes involved with eye coloring and it’s not exactly as strait forward as previously thought. Eye color, particularly the distinction of brown versus blue, involves a mutation on the OCA2 gene locus on chromosome 15. In this case, brown being the normal pigment producing allele is dominant, and blue, the mutant allele is recessive. This means that a child must receive two blue alleles to have blue eyes, otherwise they will have brown eyes.
But here’s another interesting attribute of inheritance with respect to brown and blue eyes. As stated, in order to have blue eyes, you must have two copies of the mutant form of the OCA2 allele. Therefore, two people with blue eyes could not possibly produce an offspring with brown eyes, however, two parents with brown eyes could conceivably produce offspring with blue eyes, given that both carry a single copy of the recessive allele for blue eyes.
SINGLE GENE EXPRESSION
The locus of the CFTR gene is at q31.2 on the long arm of chromosome 7. The protein the gene codes for is 1480 subunits (amino acids) long and the lack of sufficient CFTR causes mucus to be heavy and sticky and is the underlying factor in a disease called Cystic Fibrosis.. This condition can actually manifest itself in a number of chronic conditions involving multiple organs. It is a recessive trait, and like blue eyes one must inherit to alleles with the mutant CF gene to experience the disease. This is an example of a condition caused by a single gene, although to be technically accurate, some other genes may at least influence the severity of its effect.
Another factor which has to do with single gene expression or the lack thereof, is referred to as haploinsufficiency. In this case, a person may inherit one good copy and one broken copy of a gene from their parents which produces a specific protein. When the good allele for the gene, by itself, simply cannot furnish enough of the protein it codes for to support normal metabolic function, haploinsufficiency is implied.
MULTIPLE GENE EXPRESSION
In some cases, more than one specific gene must be present for a particular disease or condition to occur. An excellent example is a gene called HNF4 on Chromosome 20. Today, this gene or variants of it are known as the Type II diabetes susceptibility gene.
If you have two copies of the normal gene your chances of developing type II diabetes at any point in life are statistically irrelevant. Beyond this, understanding this gene and the implication of its variant alleles is complicated and still being studied. For instance, even if you have two variant alleles for of the HNF4 gene, this does not mean you will get type II diabetes. One reason is the HNF4 protein is not only involved with pancreatic function, but the liver and perhaps indirectly with pituitary gland function as well. Another reason, is that other proteins, the products of other genes, may be involved in how this protein is metabolized. In other words, Diabetes is a disease which may result from a specific combination of genes or perhaps even multiples of them.
Ten years ago, geneticists speculated that there were as many as a billion gene in human DNA which defined ever aspect of a person. By the time the human genome had be completely sequenced in 2000, the at number shrunk to 30,000 genes. It would seem that we are not as complicated as we first thought. Now that the human genes have been identified, geneticist around the world have been discovering new things about how they work and their effect on hereditary patterns. The laws of inheritance as we have known them for a hundred years are beginning to change and new patterns of genetic inheritance are being defined almost every day.
