Teacher guide

Predict

Chromosomes are tiny threads inside your cells that carry genes. A one-year-old boy’s blood test shows two X chromosomes (XX), a pattern doctors usually see in girls. Could a test on another part of the boy’s body give a different answer than the blood test?

Circle one. Yes / No

Watch

1. A boy whose blood came back female and his skin came back maleyoutube.com/shorts/rYCzxUn_5s0

Word of the day

Parthenogenetic chimaera (par-theh-no-jeh-NET-ik ky-MEER-uh). A body made of two cell lines, where one line grew from an egg with no DNA from a father. Also spelled chimera.

• The Chimera of Arezzo, a bronze statue the Etruscans made about 2,400 years ago, shows the monster as a lion with a goat’s head on its back and a snake for a tail.
• In Spanish, quimera can mean a pipe dream, something impossible to achieve.

Questions

1. Most people get one copy of each chromosome from mom and one from dad. The boy’s blood cells had two matching copies from his mom, and his skin cells had one copy from each parent. Which of the boy’s cells have more genetic variety, meaning more genes with two different versions?

   Circle one. His blood cells / His skin cells

   Hint. Two matching copies carry the same version of every gene. Where could a second version of a gene come from?

2. Doctors often check a person’s chromosomes with a blood sample. The boy’s blood cells tested XX, but his skin cells tested XY. What can doctors miss when they test only one part of the body?

   Hint. What would doctors have known if they’d tested only the boy’s blood?

3. Some boys have cells with two X chromosomes. Most of these boys carry a small piece of the Y chromosome stuck on one X, and that piece almost always comes from their dad. Which two test results showed that a hidden Y piece didn’t cause the boy’s XX blood?

   Hint. Look for one result about his blood and one result about his skin.

4. As of 2021, scientists had reported six people with mom-only cells, which carry DNA from a person’s mom and none from their dad. Why might doctors have trouble finding people with mom-only cells?

   Hint. Think about how often people get a chromosome test. Which part of the body do doctors usually test?

Exit ticket

Predict

Chromosomes are tiny threads inside your cells that carry genes. A one-year-old boy’s blood test shows two X chromosomes (XX), a pattern doctors usually see in girls. Could a test on another part of the boy’s body give a different answer than the blood test?

Circle one. Yes / No

Watch

1. A boy whose blood came back female and his skin came back maleyoutube.com/shorts/rYCzxUn_5s0

Word of the day

Parthenogenetic chimaera (par-theh-no-jeh-NET-ik ky-MEER-uh). A body made of two cell lines, where one line grew from an egg with no DNA from a father. Also spelled chimera.

• The Chimera of Arezzo, a bronze statue the Etruscans made about 2,400 years ago, shows the monster as a lion with a goat’s head on its back and a snake for a tail.
• In Spanish, quimera can mean a pipe dream, something impossible to achieve.

Bonus word from the video. Chromosome (KROH-muh-sohm). Chromo- comes from Greek chrōma, “color,” and -some from Greek sôma, “body.” Chromosomes are the threadlike bodies that carry a cell’s genes, named for the way they soak up dye.

Questions

1. The boy’s blood cells carried one half-set of chromosomes from his mom, copied twice. His skin cells carried one half-set from each parent. Which of the boy’s two cell lines has more genetic variety, and why?

   Hint. Think about where each copy of a chromosome came from in each cell line.

2. A blood test read the boy as XX. A skin test read him as XY. How can the boy’s blood test read XX while his skin test reads XY? And why did the blood test miss his XY cells?

   Hint. Could different tissues in one body come from different groups of cells?

3. Most boys with XX cells carry a small piece of the Y chromosome on one X. That piece almost always comes from the father’s sperm. Lisa Strain and her colleagues reported two results in 1995 that rule out a hidden Y piece in the boy. What are the two results, and how does each one rule out that cause?

   Hint. Look for one result about his blood and one result about his skin.

4. As of 2021, scientists had reported six people with a mom-only cell line, carrying DNA from the mother alone. Genetic tests usually start with blood, yet in one of the six cases, none of the white blood cells tested came from the mom-only line. How could a mom-only cell line go unnoticed? And what test would find more people with mom-only cell lines?

   Hint. Think about which tissue doctors test first and which other tissues could hold a mom-only line.

Claim, evidence, reasoning

Going further: genes from dad

1. Mouse embryos made from the mother’s DNA alone don’t survive past early development. Some genes switch on only in the copy that came from the father. Yet some mice with a mix of mom-only cells and two-parent cells survive. What two questions would help explain why the boy’s two-parent cells were important? Pick one of your questions and name the evidence a scientist would need to answer that question.

   Hint. Think about what genes from dad add. Which parts of the body might need those genes most?

Exit ticket

Watch

1. A boy whose blood came back female and his skin came back maleyoutube.com/shorts/rYCzxUn_5s0

Word of the day

Parthenogenetic chimaera (par-theh-no-jeh-NET-ik ky-MEER-uh). An individual with two cell lines, one of which developed from an egg without fertilization and carries only maternal chromosomes. Also spelled chimera.

• The Chimera of Arezzo, a bronze statue the Etruscans made about 2,400 years ago, shows the monster as a lion with a goat’s head on its back and a snake for a tail.
• In Spanish, quimera can mean a pipe dream, something impossible to achieve.

Bonus word. Chromosome (from chromo-, “color,” and -some, “body”) names a threadlike body of chromatin carrying genes in a linear order. Wilhelm von Waldeyer-Hartz coined the word in German in the late 1800s for the way chromosomes take up dye.

Predict

1. Masunaga and others, 2021, report a new patient whose body holds a mom-only cell line, made of cells carrying only maternal chromosomes. Before you read the paper by Masunaga and others, make a guess. What percent of their new patient’s white blood cells came from the mom-only line? Write one sentence on why you think so.

   Hint. Think about the boy’s blood in the video. Would every patient follow the same pattern?

Read the paper

Masunaga and others, “Parthenogenetic mosaicism: generation via second polar body retention and unmasking of a likely causative PER2 variant for hypersomnia,” Clinical Epigenetics, 2021. The paper is free to read.

Yohei Masunaga’s team reported a 28-year-old woman with parthenogenetic mosaicism, the paper’s term for a mom-only cell line, and compared her case with five earlier reports. Table 1 of the paper lists all six cases, with the boy from the video as Case 1. For each case, the table gives the other cell lines found (the mom-only line was 46,XX in all six) and the estimated share of mom-only cells in each tissue tested.

1. Quantitative reasoning Table 1 gives the mom-only share in two tissues for five of the six cases, and its last column is blank for your answers. What’s the gap between tissues, in percentage points, for each case in Table 1 with two tissues tested?

   Hint. Subtract the smaller share from the larger one. Keep words like “more than” or “about” in your answer.

2. Quantitative reasoning Genetic tests usually start with blood, and a blood test reads white blood cells. Table 1 gives a white blood cell share for every case except Case 5. For which case in Table 1 would a blood test alone have missed the mom-only line?

   Circle one. Case 1 / Case 2 / Case 3 / Case 4 / Case 6

   Hint. A blood test sees only what the white blood cells carry.

3. Quantitative reasoning In Table 1, five cases have a mom-only share for two different tissues. What do the gaps between tissues in Table 1 tell you about estimating a body-wide share of mom-only cells from one sample?

   Hint. Look at how far apart the two shares are in each case. Would one tissue give the same share as the whole body?

4. Process of science For Case 6, the authors propose that the egg kept its second polar body, which holds sister copies of the egg’s own chromosomes. In Figure 1 and the Results section, regions next to the centromeres carried one version from mom. Some regions farther out carried two different versions from mom. How does crossing over in meiosis I explain the Case 6 pattern of one maternal version near the centromeres and two farther out? And why does that pattern point to one egg instead of two merged embryos?

   Hint. Draw one pair of chromosomes with a crossover partway along. After meiosis I, which parts of the sister copies still match?

5. Information flow The Case 6 patient has idiopathic hypersomnia, a sleep disorder. Exome sequencing found a rare variant in PER2, a circadian clock gene, in 55 of 66 sequencing reads from her and in 25 of 52 reads from her mother, who has no sleep symptoms. What percent of reads carried the PER2 variant in the Case 6 patient, and what percent in the patient’s mother?

   Hint. Divide the variant reads by the total reads for each person.

6. Information flow The PER2 reads from the Case 6 patient come from a mix of mom-only cells and two-parent cells. If 70% of the Case 6 patient’s sequenced cells are mom-only cells with two variant copies of PER2, and each remaining cell has one variant copy, what percent of her PER2 reads would you predict carry the variant?

   Hint. Picture 100 cells. How many variant copies would they hold, out of how many copies in all?

7. Information flow The Case 6 patient’s mother carries one copy of a recessive PER2 variant and has no sleep symptoms. How can a mom-only cell line give a daughter two copies of a recessive variant her mother carries once?

   Hint. Think about how the mom-only line got both copies of each chromosome.

8. Science and society Masunaga and others note a bias in how doctors find people with a mom-only cell line. Genetic tests usually start with blood, and a mom-only line barely present in white blood cells would go unidentified. When should a genetics clinic test a second tissue, such as skin or saliva? And how could testing blood first skew what doctors know about mom-only cell lines? Write your answer as a one-paragraph recommendation to the clinic.

   Hint. Think about which cases a blood test finds first, and which cases never get found.

Exit ticket