HEALTH & DISEASE
HEALTH & DISEASE
GLOSSARY
alkaptonuria Rare inherited genetic disease in which the body cannot process the amino acids phenylalanine and tyrosine. The disease is caused by a mutation in the gene for an enzyme called HGD. If the child inherits two mutant copies, one from each parent, chemicals (alkapton) accumulate in the urine, turning it a dark colour that can be detected at birth.
autism Neurodevelopmental disorder involving difficulties in social interaction, communication and behaviour. Children are normally diagnosed before the age of three years old. Asperger syndrome is a milder form, with normal language and intelligence.
autoimmunity A phenomenon in which the immune system of an organism acts against its own healthy cells and tissues. Diseases caused by aberrant immune response are called autoimmune disease. Examples include coeliac disease and type one diabetes.
autosome Chromosome that is not one of the sex chromosomes (X or Y). Autosomes exist in pairs, each carrying the same genes. Autosomal dominant diseases are inherited when one copy of a gene on an autosome is mutated. Autosomal recessive diseases, however, only occur when both copies of the gene have mutations. If the two copies of a given gene are different the child is heterozygote; if they are the same the child is homozygote.
brain synapses Critical functional elements of the brain. Synapses are the points of communication between the brain cells (called neurons). The brain contains billions of neurons and each is connected by synapses to thousands of other neurons. The human brain may contain as many as 100 trillion synapses. Some synapses excite the neighbouring cell, while others can be inhibitory. Changes in synapses are important for the brain’s capacity to learn and remember.
circadian rhythm Biological process that maintains daily oscillations of about 24 hours. The 24-hour rhythm is set by an internal biological clock that is influenced by environmental conditions.
haemoglobin Protein containing iron that is responsible for carrying oxygen around the body in red blood cells. Haemoglobin carries oxygen from the lungs or the gills to the tissues of the body. Mutations in the haemoglobin gene cause diseases such as sickle cell disease and thalassemia.
Hox genes Group of similar genes that control the body plan of an embryo from head to tail. The Hox proteins determine the segment structure in the embryo, such as legs, wings in flies and vertebrae in humans. Mutations in the Hox genes can create body parts and limbs in the wrong places along the body. In many animals, the organization of the Hox genes along the chromosome is the same as the order of their expression along the length of the developing embryo (called collinearity).
HPV and cervical cancer Human papillomavirus (HPV) is a virus that has been linked to cervical cancer and genital warts. It is typically sexually transmitted. HPV is one of the most important infectious causes of cancer and may contribute to five per cent of diagnoses. In HPV-induced cancers the virus DNA can integrate into the DNA of the host cell, wreaking havoc with the mechanisms that control normal cell growth and division.
immunity Body’s biological defences to fight infection and disease. The immune system involves two components: the innate and the adaptive. The former recognizes foreign substances and reacts, while the latter involves the system of lymphocyte cells that eliminate pathogens.
immunodeficiency State in which the immune system cannot manage to fight infections. It can be caused by extrinsic factors, including viral infection or poor nutrition, but some people are born with intrinsic defects in their immune system – making them susceptible to infections. Severe combined immunodeficiency is an extreme case in which both and T and B lymphocytes are affected.
lymphocytes White blood cells in the vertebrate immune system. Lymphocytes come in different flavours, including natural killer cells (NK cells, which kill foreign and cancer cells), T cells (which can also kill) and B cells (which make antibodies).
Online Mendelian Index of Man (OMIM) Catalogue of human genes and genetic disorders and traits, with free information on Mendelian diseases and over 15,000 genes. It is particularly focused on the relationship between phenotype and genotype.
Single-nucleotide polymorphisms (SNPs) Variation in a single nucleotide at a specific position in the genome, where each variation is present to some degree within a population. SNPs cause many diseases, especially if the two variants affect protein structure and function.
SEX
the 30-second theory
Sex occurs in many different organisms, ranging from bacteria to plants and animals. Most species exist in two alternative forms known as sexes. Even in bacteria the idea of sex is similar to what is observed in more complex organisms. Organisms of different sexes produce the gametes: males produce sperm in animals or pollen in plants, females produce the ova or eggs. These are the carriers of genetic information from each parent to their offspring. Maternal and paternal gametes fuse to produce a cell that will develop into a full organism. To keep the number of chromosomes constant within a species, each gamete must carry half the amount of DNA of the organism. The process that reduces the amount of DNA is called meiosis. The sex of an organism is often genetically determined. However, there are many organisms in which sex is determined by environmental conditions. In other cases, the same organism can be first male and then female and vice-versa. And some can even be male and female at the same time. The latter are called hermaphrodites. Most female mammals, typically have two X chromosomes whereas males have XY chromosomes. The Y chromosome carries the gene that triggers maleness. In other animals, such as birds, females have the ZW chromosomes and males are ZZ.
3-SECOND THRASH
Sex allows for sexual reproduction and increases genetic variability because the egg and sperm cells carry complementary information from genetically distinct parents.
3-MINUTE THOUGHT
The separation of the sexes may have evolved from hermaphroditic organisms able to produce male and female gametes. This separation led to a specialization of the sexes to produce only one type of gametes. The driving force of sexual reproduction is that it helps spread combinations of advantageous mutations through the blending of the genetic material from both parents. This helps organisms face a changing environment.
RELATED TOPICS
See also
3-SECOND BIOGRAPHIES
AUGUST WEISMANN
1834–1914
German evolutionary biologist who proposed in 1889 the evolution of sex to create variation among siblings
CLARENCE ERWIN McCLUNG
1870–1946
American biologist who discovered the role that chromosomes play in sex determination
30-SECOND TEXT
Reiner Veitia
In humans, sex is determined as female if we are born with two X chromosomes or male if we have an X and a Y chromosome.
DEVELOPMENTAL GENETICS
the 30-second theory
How does a simple egg cell transform into a complex organism made of diverse cells such as neurons, blood cells or skin cells? Developmental biologists have devoted a great deal of attention to the problem and discovered that part of the answer lies in the genes within our genome. The gene pool of an organism is set up at fertilization and does not change over time (with rare exceptions). Therefore, all the cells in our body carry the same set of genes. But, how can cells be so different? Differences arise from variations in gene activity: for example, the haemoglobin gene is switched on in red blood cells, while photoreceptor genes are switched on in eye neurons. Developmental genetics is the study of how genes are turned on and off to control the growth and development of an organism. In developing mammal embryos a gene called HOXD3 is switched on in a special group of cells, turning them into neck cells. Some of these cells will become neurons and others muscles or vertebrae, depending on which other genes they switch on or off. Whether a cell turns on a gene, or not, depends on its position, its internal state and the external signals it receives.
3-SECOND THRASH
As organisms develop, they switch the correct genes on or off at the right time and in the right place.
3-MINUTE THOUGHT
Certain genes (called the Hox genes) are expressed in stripes spanning the body from head to tail and determine the various body parts from anterior to posterior. Amazingly, these same genes are important for specifying corresponding body parts in humans, mice and flies.
RELATED TOPICS
See also
DARWIN & THE ORIGIN OF SPECIES
3-SECOND BIOGRAPHIES
CHRISTIANE NÜSSLEIN-VOLHARD
1942–
German biologist who, with Edward Lewis and Eric Wieschaus, won the 1995 Nobel Prize in Physiology for her work on genes controlling development of the fruit fly
SEAN B. CARROLL
1960–
American biologist who argues that morphological evolution mostly arises through changes in gene expression
30-SECOND TEXT
Virginie Courtier-Orgogozo
During development, the right genes must be switched on or off for the various cells and organs to form.
BEHAVIOURAL GENETICS
the 30-second theory
Studies in fruit flies were the first to reveal the effects of genetic variation on behaviour. Genetic mutations produce proteins with abnormal functions that disrupt the development of normal behavioural responses. For example, studies of the circadian cycle identified mutations that altered the functions of the daily biological clock. Researchers also found mutations that disrupt brain synapses and affect learning and memory. Mutations in fruit flies have even been linked to courtship and mating behaviours. Behavioural genetic studies in humans are particularly challenging because of the many environmental factors affecting human behaviour. Studies comparing identical and non-identical twins can indicate possible genetic influences. Studies determine the concordance of twin pairs – that is, the percentage of pairs in which both twins share a trait. Higher concordance in identical twins compared to non-identical twins suggests a genetic influence. Studies of concordance for autism, depression and schizophrenia found 30–70 per cent among identical twins compared to 5–15 per cent for non-identical twins. These results imply moderately high levels of genetic influence. This effect could involve many genes, with the influence of each being relatively small.
3-SECOND THRASH
Genetic variation influences behavioural variation, but the levels and mechanisms of genetic involvement in behaviour variation in humans are largely unknown.
3-MINUTE THOUGHT
Genome-wide association studies (GWAS) seek to establish statistically significant associations between a variant and a trait. They can identify regions of the genome that contain genetic variants influencing human behaviour. For complex behavioural abnormalities like schizophrenia, hundreds of variants are associated with the condition. Identifying the genes near the variants that influence human behaviour is the next and most difficult challenge.
RELATED TOPICS
See also
3-SECOND BIOGRAPHIES
FRANCIS GALTON
1822–1911
English intellectual whose ideas about heredity of success led to the now discredited eugenics movement
LEE EHRMAN
1935–
American geneticist who described the relationship between genotype and reproductive success in fruit flies, paving the way for research into the genetics of behaviour
30-SECOND TEXT
Mark Sanders
How individual genes contribute to complex behavioural traits is largely a mystery.
DOMINANT & RECESSIVE GENETIC DISEASES
the 30-second theory
More than 10,000 human genetic diseases are caused by mutations of single genes. These diseases are inherited as ‘Mendelian’ traits because their inheritance follows the laws of heredity first described by Gregor Mendel. Many genetic diseases are inherited through mutations of genes carried on autosomal chromosomes – the chromosome pairs numbered one to 22 in humans. Autosomal genes can have either of two homozygous genotypes (for example, AA and aa) or the heterozygous genotype (Aa). Autosomal genetic diseases are inherited as dominant traits when one mutant allele is enough to have the disease. Diseases are autosomal recessive when two mutant copies of an allele are needed. Some genetic diseases are also caused by mutations of genes on X chromosomes. Females have two Xs and can have either of the homozygous genotypes or the heterozygous genotype. X-linked dominant genetic diseases are caused by a mutant allele on either X chromosome. X-linked recessive diseases require two mutant alleles on both female X chromosomes. In contrast, males have just one X, which expresses the trait corresponding to the X-linked allele he carries. Thus, regardless of whether the X-linked mutant allele is recessive or dominant, a male who carries the mutant allele has the disease.
3-SECOND THRASH
Genetic diseases caused by mutations of single genes on autosomal chromosomes or X chromosomes are inherited following the laws of heredity described by Gregor Mendel and by later researchers.
3-MINUTE THOUGHT
Mutations in human genes that are responsible for diseases are relatively rare. When mutant allele frequencies are polymorphic, it is likely that natural selection is responsible for their frequencies. For example, the life-threatening condition sickle cell disease occurs in the homozygous aa genotype. In malaria-rich environments, however, heterozygotes (Aa) better resist the disease than do AA homozygotes. Natural selection maintains both alleles A and a in populations.
RELATED TOPICS
See also
DNA CARRIES THE GENETIC INFORMATION
3-SECOND BIOGRAPHIES
THOMAS HUNT MORGAN
1866–1945
American geneticist who described inheritance of genes on the X chromosome based on Mendel’s laws of heredity
VICTOR McKUSICK
1921–2008
American physician and human geneticist who established a catalogue of human genetic diseases that has become the Online Mendelian Index of Man (OMIM)
30-SECOND TEXT
Mark Sanders
Genetic mutations can cause many thousands of different diseases.
GENES & IMMUNODEFICIENCY
Geneticists have discovered 300 genes that are mutated in diseases of the immune system. The incidence of such mutations is 1 in 3,000–4,000 live births. A high proportion of individuals with mutations show clinical symptoms of immunodeficiency, highlighting the key roles of these genes in immune function. Immunodeficiency disorders predispose patients to infections, autoimmunity (when the body launches immune response against its own healthy cells and tissues), inflammation, allergies and cancer. Some patients suffer from a broad susceptibility to many different microorganisms, as in severe combined immunodeficiency (SCID), while others have a surprisingly narrow spectrum of infectious susceptibility. All aspects of the immune response can be affected, including both innate and adaptive immunity, although immunodeficiency diseases frequently affect the latter. The most common genetic defects affect the production of antibodies by B lymphocytes, with the next most common involving T lymphocyte and phagocytic cell deficiencies. Early diagnosis of these disorders is important for appropriate treatment, which may include protein replacement, cell replacement, gene therapy and targeted modulation of inflammation and autoimmunity.
3-SECOND THRASH
Although they are rare, there are many monogenic diseases of the immune system – ones controlled by a single gene. These can predispose people to infections, autoimmune and inflammatory diseases, allergies and cancer.
3-MINUTE THOUGHT
Research into the molecular defects causing immunodeficiency can also teach us how the immune system works, and highlights the components of the immune system that protect us from infections. One example is the enzyme Activation Induced Deaminase (AID), which is required for making antibodies. Another is the discovery that the genetic defects that impair interferon γ production also cause selective predisposition to mycobacterial infections.
RELATED TOPICS
See also
DOMINANT & RECESSIVE GENETIC DISEASES
3-SECOND BIOGRAPHIES
ROBERT ANDERSON ALDRICH
1917–98
American paediatrician who showed that an immunodeficiency syndrome first identified in 1937 by Alfred Wiskott was passed from generation to generation through the X chromosome. The disease is known as Wiskott-Aldrich syndrome
ROBERT A. GOOD
1922–2003
American physician who is regarded as a founder of modern immunology and led the team that performed the first successful bone marrow transplant in 1968
30-SECOND TEXT
Alain Fischer
Genetic defects can affect several cell types of the immune system.
THE GENETICS OF AUTISM
the 30-second theory
Autism affects more than 1 per cent of the world’s population. People with autism have atypical social and communication skills and restricted interests – and they exhibit repetitive behaviour. Autism is not a discrete condition but rather a spectrum of behaviours. Autism rarely emerges in isolation; it usually coexists with other psychiatric and medical conditions, including intellectual disability, epilepsy, sleep disorders and gastrointestinal problems. More than 100 risk genes for autism have been identified. For some individuals, a single mutation is enough to develop autism (especially in individuals with both autism and intellectual disability). In contrast, the genetic architecture is more complex in some individuals, involving more than 1,000 genetic variations, each with a low effect, which additively increase the risk of autism. Many of the risk genes are key regulators of brain connectivity regulating the contact between neurons (the synapses). Changes in any of these proteins can increase or decrease the number and strength of the brain’s synapses and, ultimately, connections within the brain. Current research on autism explores the role of these genes during brain development. This knowledge should improve diagnosis, care and integration into society for individuals with autism.
3-SECOND THRASH
The genetics of autism differs from one individual to another, but most of the autism-risk genes regulate brain connectivity.
3-MINUTE THOUGHT
People affected by autism range from individuals with no verbal language skills to those with Asperger syndrome who have high cognitive functions. Most of our knowledge on the genetics of autism comes from studies of apparently monogenic forms of autism (those controlled by a single gene). Mice with these mutations display atypical social interaction and ultrasonic vocalization. Neurobiological studies show that synaptic plasticity – the property of synapses to respond to environmental stimuli – is different in people with autism.
RELATED TOPICS
See also
DOMINANT & RECESSIVE GENETIC DISEASES
3-SECOND BIOGRAPHIES
LEO KANNER
1894–1981
Austrian-American psychiatrist and physician who published the first cases of patients with autism
HANS ASPERGER
1906–80
Austrian paediatrician who reported the first patients with Asperger syndrome
30-SECOND TEXT
Thomas Bourgeron
Autism is a complex spectrum condition that can involve many genes. Often these genes are responsible for managing the connections between synapses in the brain.
THE GENETICS OF CANCER
the 30-second theory
Cancer is a terrible disease and one of the leading causes of death worldwide. It occurs when normal cells of the body lose control of their cell cycle, so that they divide without stopping and spread around the body. Rapidly dividing cancer cells can form growths called tumours; benign tumours do not spread, whereas malignant tumour cells can invade other tissues (a process called metastasis). Cancer is a genetic disease that results from changes in the genes that normally control how cells grow and divide. There are hereditary cancer syndromes, called germline mutations, in which genetic changes are inherited from parents and can be passed on to children. But most cancers result from genetic changes that occur over one’s lifetime. These are called somatic mutations and can be due to errors during cell division or mutations caused by exposure to chemical substances (such as tobacco smoke) or radiation (such as UV rays). Cancer mutations can activate genes that push cells to divide, called oncogenes. Alternatively the mutations can inactivate genes that prevent cell growth, called tumour suppressor genes. Knowing which genes are affected in a tumour can help doctors to tailor the treatment for a particular cancer. Genetic information also predicts cancer risk for other family members.
3-SECOND THRASH
Cancer is the most common human genetic disease, affecting young and old, rich and poor alike.
3-MINUTE THOUGHT
Although some cancer mutations are inherited, most cancers are caused by genetic changes that occur during an individual’s lifetime. Infections may be responsible for as many as one-fifth of all cancers. Experts predict that more than 30 per cent of cancers could be prevented, by reducing tobacco smoking, improving healthy living and immunization against viral infections. Cancer genetics has taught us a lot about how normal cells divide and grow.
RELATED TOPICS
See also
3-SECOND BIOGRAPHIES
THEODOR HEINRICH BOVERI
1862–1915
German biologist who first proposed the cellular processes that cause cancer
ALFRED GEORGE KNUDSON
1922–2016
American physician who first hypothesized how accumulated mutations lead to cancer
HARALD ZUR HAUSEN
1936–
Nobel Prize-winning German virologist who discovered that HPV can cause cervical cancer
30-SECOND TEXT
Jonathan Weitzman
Understanding the genes involved is key to cancer treatment.
