Genetic Conditions and Inheritance

Original Editor - Anna Fuhrmann Top Contributors - Lucinda hampton, Anna Fuhrmann, Kim Jackson and Claire Knott

Introduction

A genetic disorder is a disease caused in whole or in part by a change in the DNA sequence away from the normal sequence.

The Gene is the basic physical unit of inheritance.

• Genes are passed from parents to offspring and contain the information needed to specify traits.
• A gene is a region of DNA that encodes function.
• A chromosome consists of a long strand of DNA containing many genes.
• Genes are arranged, one after another, on structures called chromosomes.
• Humans have approximately 20,000 genes arranged on their chromosomes.

Genetic disorders can be caused by

1. A mutation in one gene (monogenic disorder),
2. Mutations in multiple genes (multifactorial inheritance disorder),
3. A combination of gene mutations and environmental factors, or
4. Damage to chromosomes (changes in the number or structure of entire chromosomes, the structures that carry genes).

New discoveries of the human genome (the complete set of human genes) find that nearly all diseases have a genetic component.

• Some diseases are caused by mutations that are inherited from the parents and are present in an individual at birth eg sickle cell disease.
• Other diseases are caused by acquired mutations in a gene or group of genes that occur during a person's life. Such mutations are not inherited from a parent, but occur either randomly or due to some environmental exposure eg cigarette smoke. These include eg many cancers; some forms of neurofibromatosis.

Image 1: An x-shaped chromosome is made up of tightly wound strands of DNA. DNA has smaller sections, called genes, which can "code" for physical traits.

Image 2: The chromosome in the nucleus contains the double helix DNA in a form coiled with histone proteins, thus significantly condensed

Image 3: Animation of the structure of a section of DNA. The bases lie horizontally between the two spiraling strands. Nitrogen: blue, Oxygen: red, carbon: green, hydrogen: white, phosphorous: orange

History

Genetics as a scientific discipline stemmed from the work of Gregor Mendel in the middle of the 19th century. Mendel suspected that traits were inherited as discrete units, and, although he knew nothing of the physical or chemical nature of genes at the time, his units became the basis for the development of the present understanding of heredity. All present research in genetics can be traced back to Mendel’s discovery of the laws governing the inheritance of traits.

Genetic inheritance / Heredity

This chapter will capture the basics about genetic inheritance. For a great introduction and visualisation about this topic see the YouTube video by the Crash Course brothers below.

Definitions

Traits

Traits - or characteristics - are observable details of an organism, e.g. in humans: one's eye colour, the shape of one's finger nails, ...

• Mendelian trait: A characteristic or trait that is determined by one gene only. This means that a specific characteristic's information is found on only one of the 23 chromosome pairs that a human DNA. Therefore, the information about this particular characteristic is linked to one specific location within the DNA. The typical example is the colour of pea plant flowers, which was the trait that Mendel examined in his experiments.
• Polygenic trait: A characteristic or trait that is a composition of information from different genes, ergo not tied to one single location within the DNA. Most traits, since they are quite elaborate, are polygenic traits.
• Pleiotropic: A gene that influences how other genes are interpreted.

To best comprehend the pathway of genetic inheritance most commonly examples of Mendelian traits are used, since the observed trait is determined by one single gene.

Chromosomes

Chromosomes are the strings made of the DNA. Humans have 23 pairs of chromosomes, each pair containing one set of genetic information from the mother and one from the father. Every cell in the human body holds 23 chromosome pairs, except for reproductive cells which only contain 23 single chromosome strings.

Genes

Genes are the "basic physical unit of inheritance" and are made of sequences within the DNA. They hold information about any type of process needed to grow, maintain and renew an organism's traits. The 23 chromosome pairs of humans hold around 20,000 genes.

Alleles

Humans have two sets of each genes, one in each of the chromosomes. A pair of genes is called an allele. These genes do not necessarily need to be the same since one of them is inherited from the mother and the other one from the father.

Genotype

The genotype is the composition of the two parentally inherited alleles.

• Heterozygous: Genotype has two alleles that are different.
• Homozygous: Genotype has two alleles that are alike.

Phenotype

The phenotype is defined as "the set of characteristics of a living thing, resulting from its combination of genes and the effect of its environment" hence the 'final result' of the composition of parentally inherited and environmentally acquired information.

Genetic inheritance pathways

Genetic abnormalities can be inherited through different pathways, depending on the location and type of the affected gene. The three types of inheritance for monogenic (single-gene) diseases are:

• Dominant [see Image 1]

When inheriting a dominant allele from one parent, this trait is the one displayed in the phenotype. A dominant allele always prevails when combined with a recessive allele.

• Recessive [see Image 2]

When inheriting a recessive allele the trait is displayed in the phenotype not if it is combined with a dominant allele. The recessive trait is only activated if both alleles are recessive and no dominant allele of this gene is present.

Image 2: Autosomal recessive inheritance of an affected gene (example of cystic fibrosis)

Image 1: Autosomal dominant inheritance of an affected gene from the father

• X-linked

The inheritance of an X-linked allele can be both dominant [see Image 3] and recessive [see Image 4].

Image 4: X-linked recessive inheritance of an affected gene from the mother

Image 3: X-linked dominant allele, inheritance of an affected gene of the mother

The Punnet Square

The Punnet Square can be used to determine the possible outcomes of traits being transferred from the parents to the offspring. An example can be found in Image 2 on the right side, which shows the probability of inheriting cystic fibrosis from two parents both carrying a recessive allele for the disease.

Diagnosis

Newborn genetic screening is a standard procedure for most babies which is conducted right after birth in many countries. It helps to identify genetic disorders at an early stage so that prevention and treatment methods can set in from the very beginning. In other cases, diagnosis includes physical examination, personal and family medical history, and laboratory testing including genetic testing.

Clinical relevance

Most common disorders

Monogenic diseases:

• Haemophilia
• Von Willebrand Disease (specific form of haemophilia)
• Thalassaemia
• Sickle Cell Anaemia
• Cystic fibrosis
• Tay Sachs Disease
• Huntington's disease

Polygenic conditions:

• Coronary Heart Disease
• Diabetes Type II
• Hypertension
• Autoimmune disorders
• Arteriosclerosis

Others:

• Down Syndrome/ Trisomy 21 (caused by an extra chromosome on the 21st chromosome pair)
• Edward's Syndrome/ Trisomy 18 (caused by an extra chromosome on the 18th chromosome pair)

Disorders most relevant for physiotherapy practice

Apart from the diseases listed above, there are a few more conditions that are of special interest for physiotherapy practice.

• Osteogenesis Imperfecta (brittle bone disease)
• Muscular Dystrophy
• Charcot-Marie-Tooth Disease

Treatment

The treatment of conditions arising from genetic abnormalities are as variant as the conditions can be. They depend very much on the area of the body that is affected by the disease. To see specifics about physiotherapy treatment of common genetic conditions, please check the above listed diseases for further information.

Useful links & further information

More extensive information about common genetic diseases can be found on the Physiopedia page Congenital and Acquired Neuromuscular and Genetic Disorders.

More details about types of genetic changes and diseases that fall under those categories can be found on the page of Stanford Children's Health.

For more information about genetic and rare diseases and an A-Z list of those diseases follow this link.

Extensive information about diagnosis of and testing for genetic diseases can be found in Understanding Genetics: A District of Columbia Guide for Patients and Health Professionals by the Genetic Alliance and the District of Columbia Department of Health which can be found here.

An explorative, short article about "Genomic medicine and the future of physiotherapy" by Jon Cornwall and Peter Osmotherly from 2014 can be found here.