Genetic Conditions and Inheritance

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

Introduction

Chromosome-DNA-gene copy

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

Chromosomes contains the DNA in a form coiled with histone proteins condensing it.

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.

For a great introduction and visualisation about inheritance see below

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.

Difference Between Genetic and Hereditary Diseases

• Genes are the materials present in our body which are responsible for transmitting traits from parents to offspring from one generation to another.
• Several spontaneous or induced gene mutations can result in defective or faulty genetic material, some of which will be acting as the basis for various types of inherited diseases, characteristically carrying these mutated changes from parents to offsprings.
• The main difference between these two terms lies in the fact that hereditary diseases have the potential of being carried from one generation to another whereas a genetic disease can either be hereditary or not, but there will always be a mutational change in the genome.

Gene Editing

DNA repair after CRISPR-Cas9 double strand break

CRISPR is a type of gene-editing technology that lets scientists more rapidly and accurately 'cut' and 'paste' genes into DNA. It is based on a targeted DNA-destroying defence system originally found in certain prokaryotes.

• Stands for "Clustered Regularly Interspaced Short Palindromic Repeats", a term that describes a family of nucleic acid sequences that were discovered in archaea and bacteria in the 1990s containing copies of virus genes. It appeared that somehow these organisms had stolen genes out of viruses, and researchers wanted to figure out why.
• CRISPR/Cas9 is a system found in bacteria and involved in immune defence. Bacteria use CRISPR/Cas9 to cut up the DNA of invading bacterial viruses that might otherwise kill them.
• This ability to identify specific DNA sequences with precision and break them apart was quickly recognised as a perfect tool for editing genes. A protein called Cas9 can be used in conjunction with engineered CRISPR sequences to hunt down codes and slice into them like a molecular scalpel, allowing geneticists to cut out a target gene, either to remove it or replace it with a new sequence.

Genetic inheritance pathways

DNA orbit animated

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:

1. Dominant: 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.
2. Recessive: 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.
3. X-linked: The inheritance of an X-linked allele can be both dominant

The Punnet Square: Used to determine the possible outcomes of traits being transferred from the parents to the offspring.

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

Diagnosis

Genetic testing is one of several tools that doctors use to diagnose genetic conditions. The approaches to making a genetic diagnosis include:

1. A physical examination: Certain physical characteristics, such as distinctive facial features, can suggest the diagnosis of a genetic disorder.
2. Personal medical history: Information about an individual's health, often going back to birth, can provide clues to a genetic diagnosis.
3. Family medical history: Because genetic conditions often run in families, information about the health of family members can be a critical tool for diagnosing these disorders.
4. Laboratory tests, including genetic testing

• Genetic testing is currently available for many genetic conditions. Some conditions do not have a genetic test. In these cases, a combination of the approaches listed above may be used to make a diagnosis.
• A diagnosis of a genetic disorder can be made anytime during life, from before birth to old age, depending on when the features of the condition appear and the availability of testing..

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:

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

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.

See also CRISPR above

Definitions

• Traits (characteristics): observable details of an organism, e.g. in humans: one's eye colour, the shape of one's finger nails.
• Chromosomes: thread like structure composed of DNA molecules tightly coiled with histone proteins. 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: 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: A pair of genes. 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 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 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.

Useful links

Physiopedia page: Congenital and Acquired Neuromuscular and Genetic Disorders.