Trait's heritability

Heritability (h²) – a note by Dr. Prabhuraj. MDS in Orthodontics.
Email: mail2prabhuraj@gmail.com

Cleft lip with or without cleft palate, dental malocclusions are caused by a complex interaction between genetic (genomic) and environmental (non-genetic) factors. Both the factors interact to develop the phenotype (nature and nurture)

“Heritability” is a statistical abstraction that, under ideal circumstances, estimates the proportion of phenotypic variation due to additive genetic effects in a particular sample from a particular time and place. In other words, heritability is the proportion of a trait’s variation that, under ideal, simplified conditions, is attributed to additive genetic variation. This ratio of additive genetic to total (additive genetic plus environmental) variation does not take into account gene-to-gene interaction or the gene-environment interaction.

h²=G/(G+E), where G is the variation of the trait’s size among individuals, as individuals have different genotypes, E is variation caused by environment, G+E is the total phenotypic variation. Allele-allele interactions at a gene locus on the chromosome is termed dominance and gene-gene interactions involving two or more loci on the chromosome is termed epistasis.

Heritability (h²) refers to a specific sample and does not necessarily pertain to the situation of a given individual, even from within the sample. It is descriptive of variances within a sample at a given time, and not much predictive. It can change with age. A different environment can alter the phenotypic expression that the genes would have promoted under other conditions. A high heritability does not necessarily prevent a trait from being substantially influenced by subsequent changes in environmental conditions in that sample.  

 Heritability estimates of dental occlusal characteristics (position, rotation and angulation) that take into account environmental covariance collectively suggest that the predominant source of occlusal variation is environmental. However, the ability of each organism to develop appropriate symmetry relies on complex genetic interactions to buffer differences in right and left symmetrical development that increase with environmental disturbances during development. Studies show that most malocclusion is acquired; there are no genes promoting crooked teeth in the vast majority of the population that experiences rotations and displacements. Identifying the environmental causes of the variation would help in interception and prevention of malocclusion. Epidemiologic studies show increased risk for cleft lip/palate with alcohol and smoking exposure during pregnancy.

Human traits (diseases or developmental anomalies) can be caused by different genetic mechanisms. An inheritance pattern could be autosomal (excludes sex chromosomes) dominant or recessive, and X-linked. The hereditary material is DNA (helical deoxyribonucleic acid molecule that constitutes the fundamental structure of a chromosome). The functional units of DNA are genes. A gene is a segment of DNA that can be copied to make RNA. An organisms basic complement of DNA is called its genome. Hereditary variation is caused by variant forms of genes (alleles). A gene that has changed from one allelic form into another has undergone mutation- an event that happens rarely but regularly.

The penetrance of a mutation, defined as the frequency of the disease triat in individuals carrying the disease mutation, will also affect the inheritance pattern. Expressivity which describes the severity of the disease, can affect the perceived inheritance pattern if the severity is so mild that the person is considered normal, when in fact they carry the disease mutation and could be identified as being affected upon careful examination or via highly sensitive diagnostic techniques.

Some traits are all caused by the same gene, meaning everyone with the triat has a mutation in the same gene. This situation is called genetic homogeneity. In contrast, there are examples in which mutations in any one of several genes will result in the same trait. This is called locus heterogeneity. Finally, some traits occur only when multiple genes are mutated in the same individual. A complex genetic trait is assumed to be caused by the combination of multiple mutations in different genes interacting with environmental factors. Thus traits can be caused by simple to complex mechanisms.

Syndromic forms of CL/P (Van de Woude Syndrome, CL/P Ectodermal Dysplasia syndrome, X-linked Cleft Palate and Ankyloglossia) often have simple Mendelian inheritance patterns and are thus more suitable for conventional genetic mapping strategies. The more common nonsyndromic CL/P has a genetically complex triat i.e, a complex inheritance pattern.

“Genetics”, as indispensable component of almost all research in biology, medicine & dental science has, classical (organismal)  and molecular (cellular mechanisms) approach, both go hand in hand.