Complex diseases

Genotypes and PhenotypesGene Expression

Factors that Affect Gene Expression

Human diseases are caused by a multitude of genetic and environmental factors acting together.

In certain conditions such as Down syndrome, genetic factors predominate, while in infectious diseases, for example, environmental factors predominate.

Most chronic non-communicable diseases such as schizophrenia and diabetes, asthma, obesity, coronary artery disease as well as some congenital malformations are caused by an interaction of both genetic and environmental factors.

Diseases that show familial clustering but do not conform to any recognized pattern of single gene inheritance are termed multifactorial disorders.

They are determined by the additive effects of many genes at different loci together with the effect of environmental factors.

What is Mendelian genetics?

Mendelian way of inheritance(dominant, recessive or sex-linked) is the way most of us studied genetics in college.

Mendelian genetics applies to rare diseases only, such as cystic fibrosis, Huntington’s disease, muscular dystrophies, etc.

These conditions render individuals unfit for breeding, which is the reason they are rare.

Common diseases such as diabetes mellitus type 2, asthma, coronary artery disease or schizophrenia are called complex diseases and their inheritance is multifactorial.

Multifactorial Diseases can be detected by association studies.

Monogenic diseases are usually detected by linkage studies.

A high probability(p) of a genetic locus being associated with a condition(red bars)- in this example EGR3 gene signals the highest ( p )value.

These conditions show a definite familial tendency but the incidence in close relatives of affected individuals is usually around 2-4% instead of the much higher figures that would be seen if these conditions were caused by mutations in single genes(25-50%).

Congenital Malformations:

-Congenital heart defects

-Neural tube defects

-Cleft lip/palate

-Pyloric stenosis

-Congenital hip displasia

Common non-communicable diseases:

-Asthma

-Schizophrenia

-Diabetes Mellitus

-Hypertension

Genes code for proteins.

Proteins determine the visible characteristic of an individual (phenotype).

The inheritance and expression of a phenotype is determined by many genes at different loci, with each gene exerting a small additive effect.

Additive implies that the effects of the genes are cumulative, i.e. no one gene is dominant or recessive to another.

Multiple genes and the environment lead to vulnerability for the schizophrenia phenotype.

Genes do not cause schizophrenia or symptoms of schizophrenia.

Genes cause subtle molecular changes in proteins and cells that may bias the individual towards psychosis.

Genes do not respect the boundaries between schizophrenia, bipolar disorder or dementia.

Enlarged lateral ventricles is a frequent endophenotype in schizophrenia.

Heritability of a trait or disease is the proportion of the total variance that is genetic.

The overall variance of the phenotype is the sum of the environmental and genetic variance.

Heritability provides information of the importance of genetic factors in the causation of a disease.

Schizophrenia 85

Asthma 80

Pyloric stenosis 75

Ischemic heart disease 65

Essential hypertension 60

Spina bifida 60

Diabetes mellitus 40