Chapter 13: Chromosomes, Mapping and the Meiosis - Inheritance Connection

Exam #4

What did Thomas Hunt Morgan discover in 1910 while working with Drosophila melanogaster?

In 1910, Thomas Hunt Morgan discovered mutant fruit flies with white eyes. Normally, fruit flies have red eyes, but he observed male flies with a white-eye mutation.

What happened when Morgan crossed a red-eyed female with a white-eyed male?

The F1 generation contained only red-eyed flies, showing that the red-eye allele is dominant to the white-eye allele.

What were the results of Morgan's F1 red-eyed female × red-eyed male cross?

In the F2 generation, he observed both red-eyed and white-eyed flies, but only males had white eyes. No white-eyed females were present.

What did Morgan initially think when he saw no white-eyed females in the F2 generation?

Morgan thought that white-eyed females might not be viable, meaning they might die before being observed.

How did Morgan test whether white-eyed females were viable?

He performed a test cross:
F1 red-eyed female × white-eyed male.
This cross produced white-eyed females, white-eyed males, red-eyed females, and red-eyed males, proving white-eyed females are viable.

What conclusion did Morgan reach from the test cross?

Because both males and females could have white eyes, Morgan concluded that the gene controlling eye color is located on the X chromosome.

Why did Morgan conclude that the eye-color gene is on the X chromosome?

Both male (XY) and female (XX) flies carry the X chromosome. Since the trait appeared in both sexes in the test cross, it indicated the eye-color gene is located on the X chromosome. This made it an X-linked gene.

How do sex chromosomes work in fruit flies?

• Females: XX

• Males: XY
  Female flies produce eggs containing only X chromosomes.
  Male flies produce sperm containing either X or Y.

• Egg (X) + sperm (X) → XX female

• Egg (X) + sperm (Y) → XY male

What is an X-linked gene?

An X-linked gene is a gene located on the X chromosome. In Drosophila, the eye-color gene is X-linked, meaning its inheritance pattern depends on the sex chromosomes.

What’s the difference between X-linked and Y-linked disorders?

X-linked disorders:

• Caused by genes on the X chromosome

• Affect both males and females, but males are more affected

Y-linked disorders:

• Caused by genes on the Y chromosome

• Affect only males

Why are Y-linked disorders only found in males, and why are X-linked disorders more common in males?

Y-linked disorders:

• Found only in males because only males have Y chromosomes.

X-linked disorders:

• Found in both males and females because both have X chromosomes.

• More common in males because males have only one X chromosome.

  • If that X has a disease-causing allele, the male will show the disorder — the Y chromosome cannot mask it.

  • Males have only one allele for each X-linked gene, so they can’t be homozygous or heterozygous — they are either normal or affected.

How do X-linked recessive disorders develop in human females vs human males?

Human females have two X chromosomes — one maternal and one paternal.
Because they have two copies of each X-linked gene, females can be:

• Homozygous dominant

• Heterozygous (carrier)

• Homozygous recessive

A female will develop an X-linked recessive disorder only if she inherits two recessive alleles — one from each parent.

A male has only one X chromosome, inherited from his mother.
A male will develop an X-linked recessive disorder if he inherits one disease-causing allele from his mom, because he has no second X chromosome to mask it.

What is the difference in how human males and females inherit X-linked disorders?

• Human males inherit X-linked disorders only from their mother, because the X chromosome always comes from Mom and the Y comes from Dad.

• Human females inherit X-linked traits from both parents, because they receive one X from Mom and one X from Dad.

What is hemophilia, and how do we know it is an X-linked recessive disorder?

Hemophilia is a blood clotting disorder in humans where the body cannot clot blood properly, causing prolonged bleeding from even minor injuries.

Hemophilia is caused by an X-linked recessive allele.
We know it is recessive because it often skips one or more generations, which is a typical pattern for recessive traits.

Since it is X-linked recessive:

• The disease allele is written as Xʰ (lowercase h).

• The normal allele is written as Xᴴ (uppercase H).

Where do human females get their two X chromosomes from, and why are both needed?

Human females have two X chromosomes:

• Xm (maternal X): inherited from the mother through the egg

• Xp (paternal X): inherited from the father through the sperm

Both X chromosomes (Xm + Xp) are necessary to form an XX zygote, which then develops into a female.

Not only human females, but females of many other species also have two X chromosomes as part of their biological sex determination system.

Where do the two X chromosomes in human females come from?

Human females have two X chromosomes:

• Maternal X (Xᴍ): inherited from the mother through the egg

• Paternal X (Xᴘ): inherited from the father through the sperm

Both X chromosomes are required for an XX zygote, which develops into a female.
(This pattern also occurs in other female mammals.)

Why does X-inactivation occur in human females, and what is a Barr body?

After an XX zygote forms, one of the two X chromosomes becomes inactivated early in embryonic development.
Reason: To prevent excess X-linked protein production, which would be lethal if both X chromosomes stayed active.

• The inactivated X becomes tightly condensed → called a Barr body.

• The active X remains decondensed → its genes are expressed.

Therefore:

• Normal human female: has 1 Barr body in each somatic cell.

• Normal human male (XY): has 0 Barr bodies, because males have only one X and it must stay active.

How does X-chromosome inactivation provide dosage compensation in human females?

In human females (XX), one of the two X chromosomes becomes randomly inactivated early in embryonic development.
This prevents the production of double the amount of X-linked proteins, which would be lethal.

The inactivated X becomes a Barr body (condensed and inactive).

• Females: 1 Barr body per somatic cell

• Males: 0 Barr bodies (because they have only one X chromosome)

This random inactivation ensures balanced X-linked gene expression between males and females.

What is dosage compensation, and how does X-chromosome inactivation prevent females from making too many X-linked proteins?

Dosage compensation is the process that balances the amount of X-linked proteins between males and females.
Since females have two X chromosomes, one X becomes randomly inactivated early in development.
This inactivated X becomes a Barr body, which prevents extra X-linked genes from being expressed.

• Females: 1 Barr body

• Males: 0 Barr bodies

Why do Calico cats show patches of black, orange, and white fur, and why are they almost always female?

• The fur-color gene is on the X chromosome and has two alleles:

  • B = black

  • b = orange

• Calico cats are heterozygous (XᴮXᵇ), so they need two X chromosomes → usually females.

• X-chromosome inactivation happens randomly in each cell:

  • If the X with B is active → black patch

  • If the X with b is active → orange patch

• When you see a black spot on a calico cat:
  The X chromosome carrying the black allele (B) is ACTIVE in that spot.
  The X chromosome carrying the orange allele (b) is INACTIVE (Barr body).
  Therefore, the fur grows in black.

• White patches come from a separate autosomal gene (S = dominant white-spotting). This gene is epistatic, meaning it controls whether fur color shows up.

Why do Calico cats have patchy black, orange, and white fur?

1. X-chromosome inactivation (Barr bodies):

   • Calico cats are female heterozygotes for the fur color gene (XᴮXᵇ):

     • B = black fur allele

     • b = orange fur allele

   • Random X-inactivation causes some cells to express black (Xᴮ active, Xᵇ = Barr body) and others to express orange (Xᵇ active, Xᴮ = Barr body).

   • Black spots appear where the X chromosome carrying black allele is active.

   • Orange spots appear where the X chromosome carrying orange allele is active.

2. Epistasis / White fur:

   • A second gene on an autosome controls whether fur color is expressed:

     • S = allows color

     • s = suppresses color (white fur)

   • Homozygous dominant (SS) cats have more white than heterozygous (Ss) cats.

✅ Conclusion:
Normal calico cats are female, and their patchy black, orange, and white fur is caused by:

• Random X-inactivation (black/orange)

• Epistasis from the autosomal white gene (white patches)

What’s the difference between X-linked and Y-linked disorders?

• X-linked: Found in both sexes, more common in males; males inherit X-linked disorders from mom, females from both parents.

• Y-linked: Found only in males; passed from father to all sons.

Why are X-linked recessive disorders more common in males?

• Males have only one X chromosome.

• If that X has a disease allele, the male will express the disorder (no second X to mask it).

What genotypes can human females have for X-linked disorders?

• Females have two X chromosomes (Xm from mom, Xp from dad).

• They can be:

  • Homozygous dominant (XX)

  • Heterozygous (Xx, carrier)

  • Homozygous recessive (xx)

• Females need two recessive alleles to express X-linked recessive disorders.

Why do females inactivate one X chromosome?

• To balance protein dosage between XX females and XY males.

• One X is randomly inactivated early in embryonic development.

• Inactivated X = Barr body (condensed, inactive).

• Active X expresses genes and produces proteins.

• Females: 1 Barr body per somatic cell

• Males: 0 Barr bodies

What are the differences between nuclear DNA and mitochondrial DNA, and how are they inherited?

Nuclear DNA:

• Found in the nucleus

• Linear and contains many genes

• Inherited from both parents (mom and dad)

• Determines identity from both parents

Mitochondrial DNA (mtDNA):

• Found in mitochondria

• Circular and contains fewer genes

• Inherited only from mom

  • During fertilization, sperm mitochondria are destroyed, so only maternal mtDNA is passed on

• Both sons and daughters have mtDNA, but only daughters can pass it to their children

✅ Usage:

• Test nuclear DNA to know both parents

• Test mtDNA to know mother only

What is nondisjunction, and how can it affect X and Y chromosomes?

• Nondisjunction = failure of homologous chromosomes (meiosis I) or sister chromatids (meiosis II) to separate properly.

• Leads to gametes with abnormal numbers of chromosomes.

What are aneuploid gametes, and what can they lead to?

• Aneuploid gametes have one extra or one missing chromosome.

• Normal human gametes have 23 chromosomes.

• Aneuploid gametes can have:

  • 22 chromosomes → missing one (monosomy)

  • 24 chromosomes → extra one (trisomy)

• Result: zygotes with abnormal chromosome numbers (e.g., Turner syndrome, Klinefelter syndrome, Jacob syndrome).

What is monosomy and how does it occur in humans?

• Monosomy = absence of one chromosome.

• Occurs when an aneuploid gamete with 22 chromosomes fuses with a normal gamete (23 chromosomes).

• The resulting zygote has 45 chromosomes.

• Zygote divides by mitosis, transmitting 45 chromosomes to all somatic cells.

• Each somatic cell in a monosomic human has 45 chromosomes instead of 46.

What is trisomy and how does it occur in humans?

• Trisomy = presence of one extra chromosome.

• Occurs when an aneuploid gamete with 24 chromosomes fuses with a normal gamete (23 chromosomes).

• The resulting zygote has 47 chromosomes (instead of the normal 46).

• The zygote divides by mitosis and transmits 47 chromosomes to all somatic cells.

• Each somatic cell in a trisomic individual has 47 chromosomes instead of 46.

How can you distinguish monosomy from trisomy in humans?

• Monosomy

  • One chromosome is missing.

  • Human has 45 chromosomes.

  • Caused when a 22-chromosome gamete fuses with a normal 23-chromosome gamete → zygote has 45.

• Trisomy

  • One extra chromosome is present.

  • Human has 47 chromosomes.

  • Caused when a 24-chromosome gamete fuses with a normal 23-chromosome gamete → zygote has 47.

What is the difference between nondisjunction in Anaphase I vs Anaphase II?

Nondisjunction in Anaphase I (Meiosis I):

• Homologous chromosomes fail to separate.

• All 4 gametes are aneuploid.

• 2 gametes have 24 chromosomes (extra).

• 2 gametes have 22 chromosomes (missing one).

• No normal gametes are produced.

Nondisjunction in Anaphase II (Meiosis II):

• Sister chromatids fail to separate.

• Half the gametes are normal (23 chromosomes).

• Half are aneuploid:

  • 1 gamete with 24 chromosomes (extra).

  • 1 gamete with 22 chromosomes (missing one).

• Produces both normal and abnormal gametes.

How to remember difference in nondisjunction in a anaphase 1 vs anaphase 2…

• Meiosis I mistake → ALL bad

• Meiosis II mistake → HALF bad

• ➡ Mistake happens early → everything after it is messed up.

• “I = ALL” → Nondisjunction in Meiosis I = ALL aneuploid gametes.

• Mistake happens later → only some are affected.

• “II = 2 bad” → Nondisjunction in Meiosis II = 2 abnormal + 2 normal.

What happens when an aneuploid gamete with an extra X chromosome fuses with a normal Y-carrying sperm? What condition does it cause and why is the individual male?

• An aneuploid gamete with an extra X chromosome (XX) fuses with a normal sperm carrying Y → forms an XXY zygote.

• XXY = Klinefelter syndrome.

Key points to remember:

• XXY individuals are genetically male because the Y chromosome determines maleness in humans.

• They are trisomic (have 47 chromosomes) because of the extra X.

• Each somatic cell has 47 chromosomes instead of 46.

• Symptoms:

  • Breast enlargement

  • Underdeveloped testes

  • Sterility

• Cause: Aneuploid gamete due to nondisjunction during meiosis.

Why are aneuploid gametes important in humans?

• Aneuploid gametes can fuse with normal gametes to produce zygotes with abnormal chromosome numbers.

• Can lead to genetic disorders such as:

  • Klinefelter syndrome (XXY) → male, 47 chromosomes, breast enlargement, underdeveloped testes, sterile

  • Other examples: Turner syndrome (XO), Jacob syndrome (XYY)

• Affect development, fertility, and physical traits.

• Show why proper chromosome separation (nondisjunction prevention) is crucial during meiosis.

How does Turner syndrome occur and what are its characteristics?

• Cause: Aneuploid gamete lacking a sex chromosome (O) fuses with a normal X gamete → XO zygote.

• Chromosome count: 45 chromosomes in somatic cells (monosomy).

• Sex: Female (only one X chromosome; normal females have XX).

• Characteristics:

  • Short stature

  • No breast development

  • Infertility

• Interesting fact: YO zygotes are nonviable.

Why is a YO zygote nonviable, while XO zygote can develop into a female with Turner syndrome?

• YO zygote formation: Egg with no sex chromosome (O) fuses with sperm carrying Y chromosome → YO zygote.

• Outcome: Nonviable; the organism cannot complete embryonic development.

• Reason: Y chromosome has only ~78 genes, mostly related to male sexual development.

  • Lacks essential genes required for embryo survival and development.

• In contrast, XO zygote (single X chromosome) can survive because X contains essential genes needed for development.

How does Jacob’s syndrome occur, and how does it affect development?

• Cause: Aneuploid sperm with extra Y chromosome fuses with normal egg → XYY zygote.

• Chromosome count: 47 chromosomes in somatic cells (trisomy).

• Sex: Male (presence of Y chromosome determines male development).

• Effect on development: Usually normal physical and sexual development.

• Key point: Not all aneuploid gametes lead to abnormal development.

How does Triple X syndrome occur, and how does it affect development?

• Cause: Aneuploid gamete with extra X chromosome fuses with normal X gamete → XXX zygote.

• Chromosome count: 47 chromosomes in somatic cells (trisomy).

• Sex: Female (two or more X chromosomes).

• Effect on development: Usually normal physical and sexual development.

• Key point: Not all aneuploid gametes lead to abnormal development.

Give two examples of aneuploid gametes that can produce individuals with normal development.

1. XYY zygote → Jacob’s syndrome (male, 47 chromosomes)

   • Extra Y chromosome

   • Usually normal physical and sexual development

2. XXX zygote → Triple X syndrome (female, 47 chromosomes)

   • Extra X chromosome

   • Usually normal physical and sexual development

✅ Key point: Not all aneuploid gametes lead to abnormal development.

What is a Barr body?

• A Barr body is an inactive X chromosome.

• It is tightly packed (condensed).

• Genes on the Barr body cannot be expressed or used to make proteins.

Which nondisjunction syndrome is nonviable?

• YO zygote is nonviable.

• It forms when an egg with no sex chromosome (O) is fertilized by a sperm with Y.

• The embryo cannot survive because the Y chromosome only has ~78 genes, most for male development, and does NOT contain essential genes needed for life.

• Therefore, YO embryos never complete development.

Can nondisjunction occur in autosomes, and which autosomal nondisjunction syndromes are viable?

• Yes — nondisjunction can occur in autosomes (chromosomes 1–22).

• Most autosomal nondisjunctions are embryonically lethal and do not result in a live birth.

• Exceptions (viable conditions):

  • Edwards syndrome (Trisomy 18)

  • Down syndrome (Trisomy 21)

What is Edwards syndrome (Trisomy 18)?

• Edwards syndrome is Trisomy 18 — individuals have 3 copies of chromosome 18 (47 total chromosomes).

• Babies with this condition are usually born alive but do not live long.

• They often die within a few months due to severe health problems such as:

  • Kidney malformations

  • Heart defects

  • Issues with other internal organs

What is Down syndrome (trisomy 21) and what causes it?

• Down syndrome is an autosomal nondisjunction disorder.

• It is caused by trisomy 21 — the individual has 3 copies of chromosome 21 instead of 2.

• Each somatic cell has 47 chromosomes (not 46).

• Individuals survive to adulthood but may have mild to moderate intellectual disability and characteristic physical traits.

• Risk increases with maternal age because the mother’s eggs and their genetic material age over time.

What is amniocentesis and when is it performed?

• A prenatal diagnostic procedure done between 14–20 weeks of pregnancy.

• A long needle and syringe are used to collect amniotic fluid containing fetal cells.

• Tests these fetal cells for chromosomal abnormalities such as Down syndrome.

• Because a needle is inserted into the uterus, there is a risk of miscarriage.

Why is the procedure called “amniocentesis”?

• Because fetal cells are taken from the amniotic fluid, the fluid that surrounds the fetus.

• Amniotic fluid contains fetal skin cells shed by the fetus.

What happens to fetal cells after amniocentesis?

• Fetal cells are isolated from the amniotic fluid.

• They are placed in a cell culture with nutrients and hormones.

• Cells divide and grow, allowing biochemical and genetic testing.

What can biochemical tests on fetal cells detect?

• They analyze gene products such as enzymes and proteins.

• Can be used to detect genetic disorders like sickle cell anemia and other metabolic or enzymatic defects.

What is sickle cell anemia?

• A genetic mutation that affects hemoglobin.

• Causes red blood cells to become sickle-shaped instead of disc-shaped.

• Sickle cells cannot pass easily through capillaries → reduced oxygen delivery → multiple symptoms.

Is sickle cell anemia always harmful?

• It can be life-threatening.

• BUT individuals who are homozygous recessive for the sickle cell gene are resistant to malaria, which is an evolutionary advantage in malaria-endemic regions.

Which chromosomal abnormalities can amniocentesis detect?

• Down syndrome (Trisomy 21)

• Edwards syndrome (Trisomy 18)

• Other autosomal and sex chromosome abnormalities

• Detection is possible because fetal chromosomes can be karyotyped.

When can fetal cells collected during amniocentesis be used for karyotyping?

About 2–3 weeks after amniocentesis, once fetal cells have grown in culture.

What type of cells are required for karyotype analysis—dividing or non-dividing?

Dividing cells.
Because chromosomes are condensed during cell division, making them visible and easy to distinguish on a karyotype.

What information can a karyotype reveal?

A karyotype can show:

• Chromosome lengths

• Large chromosomal abnormalities

• Missing or extra chromosomes (aneuploid)

• Sex of the fetus (XX or XY)

• Conditions like Down syndrome (3 copies of chromosome 21)

How is Down syndrome detected using a karyotype?

By observing three copies of chromosome 21, indicating trisomy 21.

What is karyotyping, when is it performed, and what information can it reveal?

• Definition: Karyotyping is the analysis of dividing fetal cells to examine their chromosomes.

• When: Usually 2–3 weeks after amniocentesis, performed between 14–20 weeks of pregnancy.

• Why dividing cells? Chromosomes are condensed and visible, making them easier to distinguish.

• Information revealed:

  • Number of chromosomes → detect aneuploidy (e.g., Down syndrome: 3 copies of chromosome 21)

  • Chromosome length and structure → detect abnormalities like deletions, duplications, or translocations

  • Sex determination → presence of XX or XY

What is CVS and how is it performed?

• Timing:

  • Amniocentesis: Performed at 14–20 weeks

  • CVS: Performed at 8–12 weeks (earlier)

• Where fetal cells come from:

  • Amniocentesis: Amniotic fluid

  • CVS: Chorionic villi in the placenta

• How cells are collected:

  • Amniocentesis: Syringe with a long needle

  • CVS: Flexible tube with suction

• Invasiveness:

  • Amniocentesis: More invasive

  • CVS: Less invasive

• How fast results come back:

  • Amniocentesis: 2–3 weeks for karyotype

  • CVS: Hours for karyotype

• Miscarriage risk:

  • Both have risk, but CVS is slightly less invasive

What did Mendel observe about traits, and how does this relate to genes located on the same chromosome?

• Mendel counted how many pea plants showed each phenotype (e.g., purple vs. white flowers).

• The traits he studied behaved in simple patterns because the genes he examined were on the same chromosome.

• When genes are on the same chromosome, their alleles are physically linked.

• Linked alleles tend to be inherited together because they travel together on the same chromosome during gamete formation.

What happens when two alleles are located on the same chromosome and no crossing over occurs?

• Genes located on the same chromosome are called linked genes.

• Their alleles are also located on the same chromosome, at specific positions called loci (singular: locus).

• If two alleles are on the same chromosome, they can be inherited together.

• If no crossing over occurs between them during meiosis, all gametes produced will be parental gametes.

• Parental gametes = gametes that have the same combination of alleles as the parent.

• This hypothetical “no crossing-over” scenario results in 100% parental gametes, but in reality, crossing over happens frequently.

What is a locus?

A locus is the location/position of a gene (or allele) on a chromosome.

When are only parental gametes produced?

• When two alleles lie on the same chromosome, they can be inherited together if no crossing over occurs.

• No crossing over → all gametes are parental.

• Parental gametes have the same combination of alleles as the parents.

What are recombinant gametes and how are they produced?

• Crossing over between two genes (X and Y) creates gametes with a new combination of alleles.

• These are called recombinant gametes.

• Recombinant gametes ≠ parental combination.

• When recombinant gametes fuse, they produce recombinant offspring, meaning offspring with new allele combinations.

When is crossing over more likely to occur between two genes?

• Crossing over is more likely when genes are far apart on the same chromosome.

• Crossing over is less likely when genes are close together.

• Greater distance → higher chance the chromosome will break and exchange segments between them.