D. Genetic Processes · Genetic ProcessesChromosomal Disorders: Non-Disjunction and Karyotypes
D3.4 D2.1 A1.12About 70 minutes
Learning goals- I can explain how non-disjunction in meiosis I or meiosis II produces gametes with an extra or a missing chromosome.
- I can describe trisomy and monosomy and read a karyotype to identify them.
- I can describe several chromosomal disorders: the chromosomes affected, the effects and the supports or treatments.
- I can describe structural changes to chromosomes.
Words to know
non-disjunction
The failure of homologous chromosomes (in meiosis I) or sister chromatids (in meiosis II) to separate properly.
aneuploidy
Having an abnormal number of chromosomes (one or more extra or missing).
trisomy
Having three copies of a chromosome instead of two (2n + 1).
monosomy
Having only one copy of a chromosome instead of two (2n − 1).
karyotype
An image of a cell's chromosomes arranged in pairs, used to count chromosomes and see large changes.
amniocentesis / chorionic villus sampling (CVS)
Prenatal procedures that collect fetal cells (from the amniotic fluid or from the placenta) for testing.
deletion, duplication, inversion, translocation
Structural changes in which part of a chromosome is lost, repeated, reversed, or moved to another chromosome.
When the count is off
Meiosis is precise, but it is not perfect. If chromosomes do not separate properly, a gamete can end up with an extra chromosome or a missing one. If that gamete is fertilized, every cell of the new individual will have the wrong number. Most such changes affect development so much that the embryo does not survive, but some are compatible with life and cause recognizable conditions.
This lesson describes those conditions using the scientific language of the curriculum. Behind each name are real people and families, so we will also talk about how people live with these conditions and what supports exist.
Non-disjunction
Non-disjunction means "not coming apart". It can happen at two points:
- In meiosis I: a pair of homologous chromosomes goes to the same pole. Both cells from meiosis I are abnormal, so all four gametes are abnormal: two have one extra chromosome (n + 1) and two are missing one (n − 1).
- In meiosis II: the two sister chromatids of one chromosome go to the same pole. Only that cell's products are abnormal: one n + 1, one n − 1 and two normal gametes.
When an n + 1 gamete joins a normal gamete, the zygote has 2n + 1 chromosomes: a trisomy (in humans, 47). When an n − 1 gamete joins a normal gamete, the zygote has 2n − 1: a monosomy (45). Abnormal chromosome numbers are called aneuploidy.
Worked exampleExample: Counting after non-disjunction
In a human cell, chromosome 18 undergoes non-disjunction in meiosis I. (a) How many chromosomes are in each of the four gametes? (b) If the gamete with the extra chromosome is fertilized by a normal gamete, how many chromosomes does the zygote have, and what is the condition called?
- A normal human gamete has n = 23.
- (a) Non-disjunction in meiosis I: two gametes get both copies of chromosome 18 (24 chromosomes) and two get none (22 chromosomes).
- (b) 24 + 23 = 47 chromosomes, with three copies of chromosome 18: trisomy 18.
Gametes: 24, 24, 22, 22. Zygote: 47 chromosomes, trisomy 18 (Edwards syndrome).
Reading a karyotype
To make a karyotype, technicians grow cells (often white blood cells), stop them in metaphase, when chromosomes are most condensed, stain them, photograph them and arrange the chromosomes in pairs by size, centromere position and banding pattern. Count the chromosomes, check each pair, and look at the sex chromosomes. A karyotype is written like this: 47,XX,+21 (47 chromosomes, female, an extra chromosome 21).
Some chromosomal conditions
| Condition | Chromosomes | Some typical effects | Supports and treatments |
|---|
| Down syndrome | Trisomy 21 (47,+21) | Some degree of intellectual disability (varies widely), characteristic facial features, low muscle tone; higher chance of heart differences and some other health conditions | Early-intervention therapies (speech, physical, occupational), inclusive education, heart surgery when needed, regular health check-ups. Many people with Down syndrome go to school, work and live in their communities. |
| Edwards syndrome | Trisomy 18 | Severe effects on many organs and on growth; most babies do not survive beyond the first year | Medical and palliative care; family support |
| Patau syndrome | Trisomy 13 | Severe effects on the brain, heart and other organs; most babies do not survive beyond the first year | Medical and palliative care; family support |
| Turner syndrome | Monosomy X (45,X) | Female; short stature; ovaries usually do not develop fully, so puberty may not start on its own and infertility is common | Growth hormone in childhood; estrogen therapy to start puberty; regular heart and kidney checks |
| Klinefelter syndrome | 47,XXY | Male; often taller than average; lower testosterone; usually infertile; sometimes learning differences. Many are not diagnosed until adulthood. | Testosterone therapy; educational support; fertility treatments in some cases |
| Triple X / 47,XYY | 47,XXX or 47,XYY | Often few or no noticeable effects; may be taller than average, some learning differences | Educational support if needed; many are never diagnosed |
Why are most trisomies of small chromosomes?
Chromosomes 13, 18 and 21 carry relatively few genes (18 and 21 are small; 13 is medium-sized but gene-poor). An extra copy of a large chromosome (with many more genes) usually disrupts development too much for a pregnancy to continue. Extra or missing sex chromosomes are better tolerated because extra X chromosomes are mostly inactivated (as Barr bodies) and the Y carries few genes.
Risk factors
Non-disjunction can happen in any pregnancy. The chance of trisomy 21 increases with the age of the egg, so it rises with the age of the biological mother, especially after about 35. Remember from the gamete-formation lesson that egg cells begin meiosis before birth and pause for years; one hypothesis is that the long pause makes errors in separating chromosomes more likely.
Structural changes
Chromosomes can also break and rejoin incorrectly, even when the number is normal:
- Deletion: a piece is lost. Example: cri du chat syndrome, a deletion on the short arm of chromosome 5.
- Duplication: a piece is repeated.
- Inversion: a piece is flipped end to end.
- Translocation: a piece moves to a non-homologous chromosome. A small fraction of Down syndrome cases are caused by a translocation of chromosome 21 material onto another chromosome.
Prenatal and newborn testing
People who are pregnant in Ontario may be offered prenatal screening (for example, a blood test that looks at the fetus's cell-free DNA in the pregnant person's blood, sometimes called NIPT). Screening estimates a chance; it does not diagnose. A diagnostic test such as amniocentesis or chorionic villus sampling (CVS) collects fetal cells to make a karyotype or do other genetic tests, but it carries a small risk to the pregnancy. Choices about testing are personal and are supported by genetic counsellors. You will look at the social and ethical questions in the lesson on ethics in genetics.
Hands-on activityMake and analyse a paper karyotype
You need: a printed page or a hand-drawn sheet of 46 to 47 chromosome sketches (you can copy the karyotype figure in this lesson in a random jumble onto paper), scissors (take care; a grown-up can help), glue or tape and a blank sheet.
- Have a family member draw or arrange the chromosome sketches in a jumble on a page. They may secretly add one extra chromosome or leave one out, and choose XX or XY.
- Cut out each chromosome.
- Match homologous pairs by length, centromere position and any bands drawn on them.
- Arrange the pairs from largest (1) to smallest (22), with the sex chromosomes last.
- Count the chromosomes. Write the karyotype in standard form (for example 46,XY or 47,XX,+21).
What to look for: a correct karyotype has 22 matched autosome pairs. Any chromosome without a partner, or a group of three, is the clue. This is the same reasoning (in a much simpler form) that cytogenetic technologists use in hospital laboratories.
Your turn
The failure of chromosomes to separate properly in meiosis: homologues in meiosis I or sister chromatids in meiosis II.
2Non-disjunction happens in meiosis II for one chromosome. How many of the four gametes are abnormal?
Two (one n + 1 and one n − 1); the other two are normal.
3What is the total chromosome number of a person with a trisomy? With a monosomy?
Trisomy: 47. Monosomy: 45.
4Write the karyotype for a male with Down syndrome caused by an extra chromosome 21.
5Which sex chromosome monosomy is compatible with life, and what is it called?
45,X: Turner syndrome. (A person with a Y but no X does not survive, because the X carries many essential genes.)
6Give one support or treatment for Klinefelter syndrome and one for Turner syndrome.
Klinefelter: testosterone therapy (or educational support). Turner: growth hormone or estrogen therapy (or heart and kidney monitoring).
More practice: warm-up
1Which chromosome is affected in Down syndrome?
Chromosome 21 (three copies).
2What does aneuploidy mean?
An abnormal number of chromosomes.
3What is the karyotype notation for Klinefelter syndrome?
4Name the four kinds of structural chromosome change.
Deletion, duplication, inversion, translocation.
5In which phase are chromosomes photographed for a karyotype?
More practice: on your own
1Explain why non-disjunction in meiosis I produces more abnormal gametes than non-disjunction in meiosis II.
In meiosis I the error affects a whole pair, so both cells produced are abnormal and every gamete that comes from them is abnormal (4 of 4). In meiosis II the error is in one of the two cells, so only its 2 gametes are abnormal.
2A karyotype shows 45 chromosomes, with only one X and no Y. What condition is this, and what is the person's sex?
Turner syndrome (45,X): female.
3Why are trisomies of chromosomes 13, 18 and 21 seen in newborns, but trisomy of chromosome 1 is not?
Chromosomes 13, 18 and 21 carry relatively few genes, so an extra copy can be compatible with development. Chromosome 1 is the largest, with very many genes; an extra copy disrupts development so much that the pregnancy does not continue.
4A father's sperm forms with non-disjunction of the sex chromosomes in meiosis I. What sex chromosomes could the sperm contain? What zygotes could result with a normal egg?
The X and Y stay together: sperm are XY or have no sex chromosome (O). With an X egg: XXY (Klinefelter) or X (Turner).
5What is the difference between a screening test and a diagnostic test?
A screening test estimates the chance of a condition (no risk to the pregnancy, but not a definite answer). A diagnostic test (amniocentesis, CVS) examines fetal cells directly and gives a definite answer, with a small risk.
Challenge
1Non-disjunction of the sex chromosomes in a mother's meiosis II (sister chromatids of one X fail to separate) can produce an XX egg or an egg with no X. List all the zygotes possible when these eggs are fertilized by normal X or Y sperm, and name the conditions.
XX egg + X sperm = 47,XXX (triple X); XX egg + Y sperm = 47,XXY (Klinefelter); no-X egg + X sperm = 45,X (Turner); no-X egg + Y sperm = 45,Y, which is not viable (no X chromosome).
2Why might extra X chromosomes cause milder effects than an extra autosome? Use the term Barr body.
In a cell with more than one X, all but one X is inactivated and condensed into a Barr body, so most genes on the extra X are not expressed. An extra autosome is not inactivated, so all its genes are expressed at 1.5 times the normal dose.
3A person has 46 chromosomes but has Down syndrome. Suggest how this is possible.
A translocation: extra chromosome 21 material is attached to another chromosome (often chromosome 14). The count is 46, but there are effectively three copies of the chromosome 21 genes.
Quiz
1. Non-disjunction in meiosis I results in:
2. A karyotype written 47,XX,+21 shows:
3. Klinefelter syndrome is caused by:
5. Which structural change moves a piece of a chromosome to a non-homologous chromosome?
6. Which statement about Down syndrome is accurate?
Big idea: This lesson covers the chromosomal half of D3.4: disorders caused by non-disjunction and other chromosome changes, the chromosomes involved, their effects and treatments. Mutations in single genes are in the next lesson.
Sensitive topic: Your teen may know someone with Down syndrome, Turner syndrome or another condition named here, or your family may have experience of pregnancy loss or prenatal testing. The lesson uses people-first language ("a person with Down syndrome") and stresses that effects vary and that people with these conditions live full lives with the right supports. There is deliberately no joke in this lesson.
How to help: Ask your teen to explain non-disjunction with two pencils (a homologous pair) and two hands (the poles): "What happens if both pencils go to one hand?"
Common difficulties:
- Mixing up which division error gives 4 versus 2 abnormal gametes.
- Confusing trisomy (number change) with translocation (structure change).
- Thinking screening tests give a diagnosis.