Meiosis usually delivers exactly one copy of each chromosome to every gamete, but occasionally it does not, and a single extra or missing chromosome can affect development throughout the body. Genetic mutations in a single gene can also cause disorders. Over the last few decades, scientists have learned to read chromosomes and DNA, to insert genes into bacteria, to edit genes in human cells and to grow embryos outside the body. These technologies can diagnose and treat disease and improve crops and livestock. They also raise hard questions about privacy, fairness, safety and what kinds of choices people should be able to make. This topic covers the biology first, then presents the main perspectives in those debates.
A change in chromosome number is called aneuploidy. It usually comes from non-disjunction in meiosis: a gamete with chromosomes fertilized by a normal gamete gives a trisomy (three copies, 47 chromosomes in humans), and a gamete with gives a monosomy (one copy, 45 chromosomes). Embryos missing a whole autosome almost never survive to birth, so the monosomy seen in born individuals is almost always of a sex chromosome. The chance of non-disjunction in eggs increases with the mother's age. Chromosome structure can also change: a piece can be lost (deletion), copied (duplication), flipped (inversion) or moved to a different chromosome (translocation).
| Disorder | Chromosome change | Typical physical effects | Treatment and support |
|---|---|---|---|
| Down syndrome | Trisomy 21 (47,XX,+21 or 47,XY,+21) | Intellectual disability that varies from person to person, low muscle tone, characteristic facial features, higher chance of heart defects | No cure; early intervention, therapies (speech, physical), surgery for heart defects when needed |
| Edwards syndrome | Trisomy 18 (47,XX,+18 or 47,XY,+18) | Severe developmental problems, heart and other organ defects; most affected infants do not survive their first year | Supportive and comfort care |
| Patau syndrome | Trisomy 13 (47,XX,+13 or 47,XY,+13) | Severe brain, heart and other defects, sometimes cleft lip and palate; most affected infants do not survive their first year | Supportive and comfort care |
| Turner syndrome | Monosomy X (45,X), female | Short stature; ovaries usually do not develop normally, so most are infertile | Growth hormone; estrogen therapy at puberty |
| Klinefelter syndrome | 47,XXY, male | Often taller than average, lower testosterone, usually infertile; many are never diagnosed | Testosterone therapy |
| Cri-du-chat syndrome | Deletion on the short arm of chromosome 5 | High-pitched cry in infancy, intellectual disability, small head | Therapies and supportive care |
Other genetic disorders come from mutations in a single gene rather than whole-chromosome changes. Cystic fibrosis (autosomal recessive) is caused by mutations in the CFTR gene, which disrupt the movement of chloride ions across cell membranes and lead to thick mucus in the lungs and digestive system. In 1989 a team led by Lap-Chee Tsui at the Hospital for Sick Children in Toronto, working with Francis Collins's group at the University of Michigan, identified the CFTR gene. Sickle cell disease (autosomal recessive) comes from a single base change in the gene for part of hemoglobin, which makes red blood cells deform into a sickle shape. Huntington disease is autosomal dominant, and hemophilia A is X-linked recessive.
Karyotypes and genetic screening
A karyotype is an organized picture of a person's chromosomes. To make one, cells (often white blood cells from a blood sample) are grown in the lab, and a chemical stops them at metaphase, when chromosomes are most condensed. The chromosomes are stained, which gives each one a distinctive pattern of light and dark bands, then photographed and arranged in pairs by size, centromere position and banding pattern. A typical human karyotype shows 22 pairs of autosomes, numbered 1 to 22 roughly from largest to smallest, plus the sex chromosomes (XX or XY). Extra, missing or rearranged chromosomes stand out. Karyotypes are written as the total count, then the sex chromosomes, then any change: 46,XY is typical, and 47,XX,+21 is a female with trisomy 21.
- Newborn screening — a few drops of blood from a baby's heel are tested for a set of treatable conditions. For example, early detection of phenylketonuria (PKU) lets a special low-phenylalanine diet begin before damage occurs.
- Carrier testing — shows whether a person carries one copy of a recessive allele (such as a CFTR mutation) that they could pass to children.
- Prenatal screening — ultrasound and tests of the pregnant person's blood, including tests of fetal DNA fragments that circulate in it, estimate the chance of conditions such as trisomy 21. A screening result gives a likelihood, not a diagnosis.
- Prenatal diagnostic tests — amniocentesis (sampling the fluid around the fetus) and chorionic villus sampling (sampling cells from the placenta) give cells that can be karyotyped or DNA-tested. They are more definitive but carry a small risk of miscarriage.
- Preimplantation genetic testing — used with in vitro fertilization: a few cells are tested from early embryos before one is chosen to transfer to the uterus.
Recombinant DNA, gene therapy and stem cells
Recombinant DNA is DNA that combines sequences from different sources. The classic method uses a plasmid, a small circle of DNA found in bacteria. A restriction enzyme cuts the plasmid and the human gene at specific base sequences, leaving matching ends. DNA ligase joins the gene into the plasmid, and the recombinant plasmid is put into bacteria. As the bacteria multiply, they make the human protein. Human insulin for people with diabetes is produced this way, largely replacing insulin once extracted from animal pancreases. The same idea is used to make genetically modified crops, such as corn carrying a gene from the bacterium Bacillus thuringiensis that produces a protein toxic to certain insect pests. Gene therapy aims to treat a genetic disorder by adding a working gene or editing a faulty one in a patient's cells. Genes are usually delivered by a vector, often a virus modified so it cannot cause disease. Somatic gene therapy changes only body cells of the patient, so the change is not inherited. Germline changes would affect eggs, sperm or embryos and be passed to future generations. Newer tools such as CRISPR-Cas9 can cut DNA at a chosen sequence, allowing precise edits. In 2023 regulators in the United Kingdom and the United States approved the first CRISPR-based therapy, for sickle cell disease: a patient's own blood stem cells are edited outside the body and returned. Canada has also approved it. Gene therapy also has a history of serious setbacks: in 1999 a volunteer in a US gene therapy trial died from an immune reaction to the viral vector, and in some early trials the vector inserted near genes that control cell division and caused leukemia.
A stem cell can divide to make more of itself and can also develop (differentiate) into specialized cells. Embryonic stem cells are pluripotent: they can become almost any cell type, but obtaining them destroys an early embryo. Adult (somatic) stem cells, such as the blood-forming stem cells in bone marrow, are multipotent: they make a narrower range of cell types. Canadian researchers James Till and Ernest McCulloch demonstrated blood-forming stem cells in mouse bone marrow in 1961 at the Ontario Cancer Institute in Toronto. Bone marrow (stem cell) transplants are now an established treatment for some blood cancers. In 2006, Shinya Yamanaka's team showed that adult mouse cells could be reprogrammed into induced pluripotent stem cells (iPSCs), which avoids using embryos.
Reproductive technologies, diversity and ethics
- Artificial insemination — sperm is placed in the female reproductive tract without mating. It is widely used in livestock, especially dairy cattle, and frozen semen can be shipped around the world.
- In vitro fertilization (IVF) — eggs are fertilized by sperm in a lab dish and resulting embryos are transferred to the uterus. The first baby conceived by IVF was born in England in 1978.
- Embryo transfer — embryos from a genetically valuable female are placed in surrogate females, so one animal can have many offspring.
- Cloning by somatic cell nuclear transfer — the nucleus of a body cell is placed into an egg whose own nucleus was removed. Dolly the sheep, born in 1996 at the Roslin Institute in Scotland, was the first mammal cloned from an adult cell. A clone is genetically identical to the nucleus donor.
These technologies can work in both directions for genetic diversity. They can increase it: frozen semen and embryos let breeders bring alleles from distant populations into a local herd, gene banks store sperm, eggs, embryos and seeds from rare breeds and varieties, and recombinant DNA can add genes from another species. They can also decrease it: when many farms use semen from a small number of top-performing sires, much of a breed shares the same few fathers, and cloning produces genetically identical individuals. A population with less genetic diversity is more vulnerable to a new disease or a changing environment, so breeders and conservation programs track diversity carefully.
| Technology | Arguments made in support | Concerns raised |
|---|---|---|
| Genetic screening and testing | Allows early treatment (newborn screening); lets people make informed reproductive and health decisions | Privacy; possible discrimination by insurers or employers; anxiety from uncertain results; some disability-rights advocates argue prenatal screening can send a message that lives with disability are less valued |
| Gene therapy and gene editing | Could treat or cure serious inherited disorders that have no other treatment | Safety and unknown long-term effects; very high cost and unequal access; germline editing would affect future generations who cannot consent, and could be used for enhancement rather than treatment |
| Embryonic stem cell research | Could lead to treatments for injuries and diseases; helps explain development | Some people, for religious or philosophical reasons, hold that a human embryo has moral status that should protect it from destruction; others hold that early embryos do not have that status |
| IVF and preimplantation testing | Helps people with infertility have children; can avoid passing on a serious disorder | Cost and access; what to do with unused embryos; worries about choosing embryos for non-medical traits |
| Cloning and genetically modified organisms | Can preserve valuable or endangered animals; can increase crop yields or reduce pesticide use | Animal welfare; loss of diversity; ecological effects of modified organisms; who owns patented organisms |