Introduction to genetics, part 1

In light of the importance of understanding genetics for understanding the tendency of mental illnesses (and personality traits in general) to have certain biological and genetic bases, an introduction to basic genetics is instructive.

But what is a gene? A gene is simply a unit of heredity. They possess instructions which go into constituting our blueprint, and are responsible for determining human characteristics. They come in pairs and are made from material called "DNA," or deoxyribonucleic acid. While genes contain instructions or blueprints, these instructions can go wrong. A change in these instructions is called a mutation. These mutations change the instructions and produce consequences contrary to the 'intention' of the original blueprint. Residing in a "locus," different versions of genes are known as 'alleles.' For example, an eye color gene may have a blue allele, a brown allele, etc. Genes can be found in thread-like structures in a cell's nucleus called 'chromosomes.'

As is well-known, the DNA molecule is structured as a double helix, with both strands being constituted by phosphates and sugars. It consists of three main parts:

1) Five-carbon sugar (deoxyribose)

2) Phosphate molecule

3) One of 4 nitrogen-containing bases.

a. Adenine (A)

b. Cytosine (C)

c. Guanine (G)

d. Thymine (T)

Each of these letters make up one of the bases of the message encoded in DNA. Structured like a ladder, these bases make up the 'rungs' of the DNA ladder.

DNA codes for proteins. It replicates itself into two identical copies and is then transcribed into RNA. This RNA is translated by tRNA in order to produce proteins; a process known as the "central dogma." RNA IS composed of a four-letter alphabet, like DNA, consisting of, with the "thymine" (T) replaced by a uracil (U). Its messages consist of "codons," which is a kind of three-letter word.

These codons code for specific amino acids, amino acids being the building blocks of proteins. When we know the sequence of bases in a gene, we can predict codons and the correlated amino acid sequence of the protein for which the gene codes. There are 24 of these amino acids, most of which can be coded for by more than one codon. A coding seqeunce is first signaled by a "start codon," which is a unique sequence whose purpose is to begin the coding sequence (this codon also codes for a methionine). Codons which code for the end of an amino acid sequence are called "stop codons." There are three of them.

As noted before, codons consist of three letter words. It is through these that the RNA message (mRNA) is read. Amino acid sequences are constructed sequentially acocrding to the distinct instructions in the RNA, and these sequences create a protein chain as the message is read. These codons signal for specific amino acids to be added to the protein chain being constructed. For example, an RNA message that reads GUGGAGUUU would code for a protein chain of valine, glutamic acid and phenylalanine.

In translating the RNA message (mRNA), something called transfer RNA (tRNA) brings the relevant amino acid to the template of the mRNA. tRNA contains complementary RNA codes. This process issues in the sequential addition of amino acids to form a polypeptide chain.

Next, let's look at chromosomes. As noted before, chromosomes are the regions in which genes reside. There are 23 pairs of these chromosomes in humans, making up 46 chromosomes, the first 22 of which are known as "autosomes." These are numbered 1-22. The 23rd pair determines the sex of the individual. Two chromosomes make a female and one X and one Y creates a male. By means of a karyotype (a picture of chromosomes), we can helpfully arrange chromosomes by size. Each member of each chromosome pair (normally) comes from each parent.

Chromosomes possess a structure called a centromere, at which the two 'arms' of the chromosome are joined. The short arm of the centromere is called the 'p arm,' from the French word petit, meaning 'small,' and the long arm is known as the q arm because it comes after p in the alphabet. The ends of chromosomes, on the other hand, are known as telomeres.

As known before, alleles are different forms of one gene, represented by different DNA codes. Humans have two alleles of all autosomal genes. Keeping in mind that the wild genetic variation we witness in humans is caused by alterations in the DNA code, these changes come in different forms, and consist of changes to individual base pairs. Examples of such changes include "insertions," "duplications" of specific segments of DNA, inversions of pieces of DNA and deletions.

These allelic variants are known as mutations and may impart either a selective advantage or disadvantage in a population or individual. A well-known example is the sickle cell anemia, which protects its carriers from malaria. Natural selection dictates that advantageous mutations are more likely to be passed on and disadvantageous mutations will be eliminated.

There are different kinds of mutations:

1) Point mutation - a change in a single base pair. There are distinct forms of point mutations.

a. Missense mutation - a single base pair substitution results in a change in the amino acid coded for by that codon. This amino acid alteration may alter the protein enough to produce structural instabilities or abnormalities in the protein.

b. Nonsense mutation - this results in a premature stop codon, ending the mRNA translation. This halts the translation of the mRNA into a protein before its 'intended' completion and produces either abnormally shaped proteins, changing its function, or a highly unstable protein that quickly degrades..

We can think of a nonsense mutation as a kind of incomplete sentence. "The person has," instead of "The person has a brown eye." Note that the translation of the mRNA into a protein has prematurely stopped. On the other hand, a missense mutation is something like "The person has a drown eye" instead of "The person has a brown eye." It is a kind of "spelling error" in the mRNA cause by a single base pair substitution.

Genes can mutate by virtue of either deletions or the insertion of nucleotide bases. There are various forms of insertions and deletions.

1) Frameshift mutations - these occur when the number of deleted or inserted pairs is not, as they ought to be, a multiple of three. Keep in mind that codons are constituted as three base pairs. If we have a codon with only one or two base pairs, because one or two are deleted, the way the DNA is read is altered. Following the occurrence of the mutation, the following amino acids will be different, producing either an abnormal protein or simply the lack of a protein.

2) In-frame mutation - these occur when the resulting deletion or insertion produces base pairs consisting of a multiple of 3. This is a less drastic mutation, and may only result in a change of a couple of the amino acids, leaving space for the possibility of a functioning protein with a nonetheless slightly different sequence.

An allelic variation resulting in an observable difference is known as a phenotype, such as eye color or hair color. The complementary genotype, on the other hand, is the genetic makeup of the organism at its locus.

As diploid organisms, humans possess two alleles at each autosomal locus. The genotype consists of pairs of alleles, one of which is taken from the father and the other being taken from the mother. Take, for example, the esickle cell locus. There are two (main) alleles here: The S allele and the A allele. The individual's genotype consists of various combinations of these alleles. The AS genotype produces one phenotype, and the SS genotype produces another phenotype.

We speak of a "heterozygous" individual as one who possesses two different alleles at one locus (The AS genotype from our previous example, for example) whereas a homozygous individual possess identical alleles at a locus (the AA or SS genotype from our previous example, for example).

A "pedigree" is like a family tree whose biological relationships are indicated in how the individuals are connected. Males are represented as squares and females by circles, with deceased individuals being represented by slashes drawn throught hem.

We shade individuals affected by whatever genetic disorder is being analyzed. A single generation is represented by a horizontal row, with horizontal lines connecting individuals who have produced children together, and vertical lines connecting them to their children. We speak of the "proband" as the one, usually affected by the disorder being discussed, who has brought the question of the genetic disorder and its heritability to the attention to the researcher.

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