Introduction and Mendel's Laws of InheritanceChapter 1

The question that crops in our mind is about what are the substrates that actually determine the characters in an individual. The characters, in fact, are determined by certain factors called genes; the fundamental units of inheritance. For details about genes refer to Chapter 4. The genes determining specific characters in an individual are transmitted to them physically through gametes of the parents. The individual in turn passes these traits onto its offsprings through his or her gametes. An individual is either short or tall in stature or with black or blond hair entirely due to the presence or absence of specific genes responsible for a particular character or trait. Since an individual receives genes from parents (through sperm and ovum), he or she inherits characters both from the father and the mother. An important fact about gene transmission is that when they are transmitted from one generation to the next, the transmission of a trait is not random but it follows some discreet statistical laws depending upon the type of the character and of course, the behavior of the gene during gamete formation. Therefore the science of genetics can be defined as the study of genes and of the principles that govern the passage of genes from one generation to the next.

The multifactorial disorders follow different pattern of inheritance as compared to single gene disorders (Chapter 6).

The head and neck region are very common sites for carcinomas in general and oral cancer are the ones 6seen quite frequently. The dynamics of cancer involves changes in the genome that result in uncontrolled cellular proliferation and metastasis. The Growth factor and growth factor receptor genes regulate the proliferation of cells. Genes responsible for cancer are known as oncogenes. These genes function normally in regulating cellular activity. A mutation in these genes may trigger them to acquire oncogenic properties. Cell division is strictly under genetic control and each of the steps is under constant surveillance of cellular mechanisms. Cell cycle checkpoints exist at appropriate transition points of the cell cycle. The activities at these checkpoints are executed by special proteins that are synthesized by specific genes like the p54 gene. Anomalies in these genes lead to abnormal cell division and subsequently to tumor formation. Structural integrity of the DNA is determined and checked at the checkpoints before allowing it to proceed to subsequent stages of cell division. Mutations of the checkpoint controlling genes and proteins cause several cancers. The tumor suppressor genes constitute another important cell cycle controlling element. These genes apply brakes to the events in a cell division in case of detection of an abnormality at any stage. These genes are constitutively active or in simple terms, active by default in all normal cells. A mutation causing abnormal activity of any tumor suppressor gene may lead to cancer. Researchers have also identified several tumor-forming genes that occur in normal cells but remain inactive by themselves. Such proto-oncogenes trigger unwarranted cell division if they are activated by any means or when any normally occurring inhibition acting on them is withdrawn (Refer Chapter 16 for Genetics of Cancer).

It is hoped that the near future will witness a lot of exciting advances in: Use of primary teeth as source of stem cells, tissue engineering in dentistry, use of saliva as a diagnostic fluid in detecting genetic dental disorders and salivary gland gene transfer. It is quite imperative that dental practitioners now will increasingly require knowledge of human genetics and the awareness of the applications of new molecular-based diagnostic and therapeutic technologies. Thus a sound knowledge of genetics will definitely improve the ability of dentists to diagnose and treat patients suffering from inherited and genetically caused dental diseases.

Since recent past more and more diseases are being recognized as having something related to genes and genetics. This is perhaps due to interpretations based on our new and expanding knowledge at the molecular level and progress in modern diagnostic techniques. On other hand this may also be due to the fact that owing to the overall improvement in hygiene and health care, the incidence of communicable diseases and nutritional deficiency has reduced thereby shifting our attention to diseases resulting from gene-related etiology. Genetic disorders are now considered significant causes for disease in all age groups.

Mendel's work did not get recognition during his lifetime. He passed away in 1884, much before his monumental work immortalized him as the ‘father of modern genetics’.

And when these two varieties of plants (tall and short) were crossed, Mendel observed that:

Similar to the experiments in monohybrid crosses related to the height of the stem of plants, Mendel conducted experiments with other contrasting characters such as the shape and color of the seeds and pods, etc. (Table 1.1) and remarkably got statistically comparable results.8

Each of the factors (genes, as we know them today) is responsible for a trait and is located at identical positions on each chromosome of a particular pair of chromosomes (homologous chromosomes). The fixed position on a particular chromosome for a definite gene is called the locus (plural loci) for the gene.

The same positions (loci) on two homologous chromosomes contain genes responsible for the same character. For example the loci representing the height of a plant may contain genes responsible for tallness (T) or dwarfness (t) in different combinations as (TT, Tt or tt). The alternative form of genes, e.g. ‘T’ and‘t’ present at the same locus are called allelomorphs or alleles. The alleles define a particular character depending upon their dominance with respect to each other. Homologous chromosomes carrying identical alleles (same genes) are termed homozygous. A situation with different genes at the loci defining a particular trait is called heterozygous (Fig. 1.2).

Each of the gametes carries only a single chromosome out of the homologous pair. A single gamete will carry a single locus containing either a dominant or a recessive gene depending on the chromosomal constitution of the individual parent (Fig. 1.3).

Punnett squares are grids that are extensively used to compute the genetic constitution of an individual by entering the constitution of the gametes on the top and side squares of the grid. Analyzing the above shown cross that is same as the first cross in Mendel's monohybrid cross experiment to yield the first filial generation in the Punnett square, looks like as below.

The genotype of an individual is defined as its genetic constitution for any particular trait. The term phenotype denotes the physical appearance for a particular trait. A gene is considered to be a dominant if it is able to express itself in the phenotype even when it is present in a heterozygous condition, e.g. the gene for tallness ‘T’ in (Tt). The gene for shortness‘t’ is only expressed when it is present in a homozygous state (tt) in an individual and is called a recessive gene.

It is thus evident that all the progeny tall plants of the F1 generation (Tt) have different genotypes than the pure bred parent tall plants (TT) though they are same in their phenotypes.

Self-pollination of F1 plants can be analyzed in the F2 generation with the Punnett square as shown in Figure 1.6.

Self-pollination in the F1 generation yielded the F2 progeny. The F2 progeny constituted two varieties of phenotype with the reappearance of short stature in the plants. The genotype of the tall plants showed two varieties; the homozygous tall and the heterozygous tall plants. The concepts of dominance and recessive perspectives are also clear from the results in the grid squares. Characters are transmitted from one generation to next following statistical laws. When the plants of F1 generation were self-pollinated both tall and short plants appeared in the ratio of 3:1. When the plants of F2 generation were self-pollinated the tall and short plants always appeared in the fixed ratio (Figs 1.1 and 1.7).

The results of the F3 generation in the Punnett square show the genotype and the phenotype of the individual progeny.

Mendel found that in F1 generation all plants were yellow with round seeds indicating that the yellow color and the round shape as were dominant over the green color and the wrinkled shape that were recessive in nature.10

On self-pollination, the F1 plants yielded the F2 progeny. These offsprings were of four different phenotypes in the ratio 9:3:3:1 with 9 yellow and round, 3 yellow and wrinkled, 3 green and round and 1 green and wrinkled types of seeds.

It was thus observed that the two pairs of contrasting characters actually were transmitted independent of each other. The offsprings even demonstrated the new combination of characters in the form of yellow and wrinkled and green and round seeds in the F2 generation. The details of the experiments and their discussion are not discussed here.

Carl Correns, one of the rediscoverers of Mendel's work in 1900, promoted the ideas of Mendel as the “laws of inheritance”. Following three concepts are recognized as Mendel's Laws.

The dihybrid cross experiments yielded four different phenotypes in the F2 generation with yellow-round, yellow-wrinkled, green-round and green-wrinkled seeds. This implied that the genes responsible for yellow and green colors and round and wrinkled shapes of seeds separated out independently that resulted in four different phenotypes and 9 different genotypes in the F2 generation.