Inheritance
1Why this matters
Mr. and Mrs. Okafor are both healthy. Their first child, a son, was diagnosed with cystic fibrosis after newborn screening, and his older sister wants to know if she could pass it on. Their genetic counselor draws a simple two-by-two grid on a notepad and, in a few minutes, gives the family three numbers: the chance their next child is affected, the chance a healthy child is a carrier, and the chance for their daughter's own children. This page teaches that grid and the rules behind it.
2What this builds on
3Quick check before you start
1. What is an allele?
- One version of a gene
- One of the two strands of DNA
- A chromosome with no partner
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An allele is one version of a gene. You carry two copies of each autosomal gene, one from each parent, and they may be the same allele or different ones.
- Correct: One version of a gene:
- One of the two strands of DNA:
- A chromosome with no partner:
2. In which division of meiosis do homologous chromosomes separate?
- Meiosis II
- Meiosis I
- Both divisions equally
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Homologs pair and then separate in meiosis I; sister chromatids separate in meiosis II. That separation of homologs puts the two alleles of each gene into different cells.
- Meiosis II:
- Correct: Meiosis I:
- Both divisions equally:
3. A person with type AB blood carries which antigens on their red cells?
- Neither A nor B
- A only
- Both A and B
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Type AB red cells carry both the A and the B antigen, which is why type AB plasma has neither anti-A nor anti-B.
- Neither A nor B:
- A only:
- Correct: Both A and B:
4How it works, step by step
- Each body cell carries two alleles of every autosomal gene, one on each homologous chromosome.The pair of alleles, the genotype, can be homozygous or heterozygous.
- In anaphase I of meiosis, homologous chromosomes move to opposite ends of the cell.Each gamete receives only one allele of each gene, with a 1 in 2 chance for each (the law of segregation).
- Any egg can be fertilized by any sperm.A child's genotype is a random combination, and a Punnett square lists each equally likely combination.
- The two alleles in a child interact: one may mask the other, both may show, or the heterozygote may be in between.The genotype is expressed as a phenotype (dominant, recessive, codominant or incompletely dominant), which the environment can also change.
- Alleles on the X chromosome have no partner in a male.X-linked recessive traits show in males with one copy, so they affect many more males than females.
5Core concepts
6A common mistake
The wrong idea: A dominant allele is stronger, so it becomes more common over the generations, and a 1 in 4 risk means exactly one affected child in every four.
What actually happens: Dominance describes how two alleles behave in one person for one phenotype, not how common an allele is: polydactyly is dominant but rare, and the O allele is recessive but the most common ABO allele. And a Punnett square gives a chance for each child. Gametes are formed fresh for every pregnancy, so two carriers who already have an affected child still face a 1 in 4 chance with the next.
7Check yourself
Anything you miss goes into your review queue.
1. Both parents are healthy carriers of cystic fibrosis, an autosomal recessive disease. What is the chance that their first child has cystic fibrosis?
- 1 in 2
- 3 in 4
- 1 in 4
- 0
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Each carrier (Cc) makes C and c gametes equally. The Punnett square gives 1 CC : 2 Cc : 1 cc, and only cc has the disease: 1 in 4.
- 1 in 2: 1 in 2 is the chance that a child is a carrier (Cc), not that the child is affected.
- 3 in 4: 3 in 4 is the chance that a child is healthy.
- Correct: 1 in 4: Correct. One box in four is cc.
- 0: Healthy carriers each hide one disease allele, and a child who gets both has the disease, so the chance is not zero.
2. Two carrier parents have a son with cystic fibrosis and a daughter who is healthy. What is the chance that the healthy daughter is a carrier?
- 1 in 4
- 1 in 2
- 2 in 3
- 3 in 4
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The square gives CC, Cc, Cc and cc. The daughter is healthy, so she is not cc; that leaves three equally likely boxes, two of which are Cc. Her chance of being a carrier is 2 in 3.
- 1 in 4: 1 in 4 is the chance of being affected, which she is not.
- 1 in 2: 1 in 2 is a carrier's share of all four boxes. Once you know she is healthy, the affected box is removed.
- Correct: 2 in 3: Correct. Two of the three healthy boxes are carriers.
- 3 in 4: 3 in 4 is the chance of being healthy for any child before you know the outcome.
3. A couple who are both carriers of sickle cell disease already have one affected child. They say the next three children should be unaffected, because the risk is 1 in 4. What is the chance their next child has sickle cell disease?
- 0
- 1 in 3
- 1 in 4
- 1 in 2
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Gametes are formed fresh for every pregnancy, and each pregnancy is an independent draw. The 1 in 4 applies to each child, whatever happened before.
- 0: Earlier children do not use up the risk. Each pregnancy starts again at 1 in 4.
- 1 in 3: There is no reason for the risk to change after one affected child; the parents' genotypes are the same.
- Correct: 1 in 4: Correct. The chance is 1 in 4 for every child of two carriers.
- 1 in 2: 1 in 2 is the chance of a carrier child, not an affected one.
4. A type A mother and a type B father have a type O child. The father doubts the child is his. What is the best explanation?
- A type O child cannot have a type B father
- The child's blood type changed after birth
- Both parents are heterozygous, AO and BO, and each passed on O
- O is dominant, so it can appear from any parents
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Type A can be AO and type B can be BO. If each parent passes the O allele, the child is OO, type O. From an AO × BO cross, each child has a 1 in 4 chance of type O.
- A type O child cannot have a type B father: A type B father who is BO can pass on O. The blood types fit him being the father.
- The child's blood type changed after birth: Blood type is set by the genotype and does not change after birth.
- Correct: Both parents are heterozygous, AO and BO, and each passed on O: Correct. Two heterozygous parents can each pass on the recessive O allele.
- O is dominant, so it can appear from any parents: O is recessive, not dominant. It shows only when a child has two O alleles.
5. A person with sickle cell trait makes both normal and sickle hemoglobin, has red cells that sickle only under severe oxygen shortage, and has no disease. What does this show about dominance?
- The sickle allele is dominant over the normal allele
- The pattern depends on which phenotype you measure
- The normal allele is codominant at every level
- Sickle cell trait is an X-linked pattern
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At the level of hemoglobin molecules the alleles are codominant; at the level of red cell sickling, the heterozygote is in between; at the level of disease, the sickle allele is recessive. Dominance describes a relationship for one phenotype.
- The sickle allele is dominant over the normal allele: Being expressed is not the same as being dominant. The heterozygote has no disease, so for disease the sickle allele is recessive.
- Correct: The pattern depends on which phenotype you measure: Correct. Each level of phenotype shows a different pattern.
- The normal allele is codominant at every level: Both alleles are expressed at the molecule level, but the heterozygote has no disease, so the pattern is not codominant for disease.
- Sickle cell trait is an X-linked pattern: The hemoglobin gene is on an autosome, and the trait occurs equally in both sexes.
6. A man with hemophilia A and a woman who does not carry the allele have children. What should they expect?
- Half their sons affected and half their daughters carriers
- All their sons affected
- No affected children, but every daughter a carrier
- Half of all children affected, whatever their sex
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The father gives his X, with the hemophilia allele, to every daughter and his Y to every son. Daughters get a normal X from their mother too, so they are carriers; sons get their X from their noncarrier mother, so they are unaffected.
- Half their sons affected and half their daughters carriers: That is the pattern for a carrier mother and an unaffected father, the reverse of this family.
- All their sons affected: A son receives his father's Y, not his X, so the father cannot pass hemophilia to his sons.
- Correct: No affected children, but every daughter a carrier: Correct. Father-to-daughter passing makes all daughters carriers; sons are spared.
- Half of all children affected, whatever their sex: Half of all children affected describes an autosomal dominant allele, not an X-linked recessive one.
7. Compare a woman who conceives at 40 with the same woman had she conceived at 25. Predict the change in each variable.
| Variable | Change |
|---|---|
| Chance of nondisjunction in her oocytes | — |
| Risk of a child with trisomy 21 | — |
| Chance that a child of hers and a carrier partner has cystic fibrosis, if she is a carrier | — |
| Number of chromosomes in her body cells | — |
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Maternal age raises the risk of chromosome-number errors because oocytes wait decades in meiosis I and the proteins holding their chromosomes together weaken. It does not change the 1 in 4 risk from two carriers of a recessive allele.
- Chance of nondisjunction in her oocytes: up. Her oocytes have been paused in meiosis I for 15 more years, and the proteins holding their paired chromosomes together have weakened further.
- Risk of a child with trisomy 21: up. More nondisjunction gives more oocytes with an extra chromosome 21, raising the risk from about 1 in 1,200 to about 1 in 100.
- Chance that a child of hers and a carrier partner has cystic fibrosis, if she is a carrier: no change. Segregation of a single gene's alleles is 1 in 2 per gamete at any age, so two carriers still face a 1 in 4 chance.
- Number of chromosomes in her body cells: no change. Her own body cells stay at 46; age affects the separation of chromosomes in oocytes, not her karyotype.
8. A 24-year-old woman has a baby with Down syndrome. The karyotype shows most of an extra chromosome 21 attached to chromosome 14. What is the best next step for the family?
- Karyotype both parents to look for the rearrangement
- Nothing; her risk next time is the low risk for her age
- Test the baby for cystic fibrosis
- Tell her the risk rises only after age 35
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This is translocation Down syndrome. It does not depend on maternal age, and it can be inherited from a parent who carries the rearrangement without symptoms. If a parent carries it, the risk in later pregnancies is much higher than the age-based risk.
- Correct: Karyotype both parents to look for the rearrangement: Correct. A parent may be a balanced carrier of the translocation.
- Nothing; her risk next time is the low risk for her age: The age-based risk applies to Down syndrome from nondisjunction. A translocation may come from a parent, which can raise the risk sharply.
- Test the baby for cystic fibrosis: Cystic fibrosis is a single-gene disease and has nothing to do with this karyotype.
- Tell her the risk rises only after age 35: Translocation Down syndrome is not tied to maternal age, so her age does not set her risk.
8Summary
Your genotype is the pair of alleles you carry for a gene; your phenotype is what shows, and the environment shapes it too. Homozygous means two identical alleles, heterozygous two different ones, and a gene with multiple alleles, like ABO, still gives each person only two. A dominant allele shows with one copy, a recessive one only with two, so carriers of recessive diseases are healthy heterozygotes. Segregation in meiosis I sends one allele into each gamete, and a Punnett square gives the chance for each child: 1 in 4 affected from two carriers, 1 in 2 from one heterozygous parent with a dominant disease. In incomplete dominance the heterozygote is in between; in codominance (type AB) both alleles show. X-linked recessive traits affect mostly males, pass from carrier mothers to half their sons and never from father to son. Polygenic traits like height form a bell curve. Chromosomal disorders, seen on a karyotype, include trisomy 21, Down syndrome, whose risk rises with maternal age.