Phillips - Genetics

Question 1

Gametogenesis

Answer 1

• Devo of eggs (ova) or sperm from primordial germ cells -> both require meiosis, but difference in TIMING (and other details)
• Germ cells originate in endoderm of the yolk sac at the 4th week of embryonal life
• 6th week: migrate to genital ridge, and associate with somatic cells to form the primitive gonad
• Gonad differentiates into ovary or testis in accordance w/sex-determining genetic guidance

Question 2

SRY

Answer 2

• Sex-determining region on the Y chromosome
• 46 XY: SRY presence indicates that indifferent gonad will become testis
  1. Leydig cells -> testosterone
  2. Sertoli cells -> AMH (SALT memory tool)
• 46 XX: NO SRY
  1. Indifferent gonads default to ovary
• Not the only sex-determining gene, but the most important one

Question 3

46 XY F discovered to have a mutation in SRY. What does this mean?

Answer 3

• Mutation in SRY causes gonad to remain an undifferentiated that will not produce any hormones

Question 4

What are the 2 purposes of meiosis?

Answer 4

• Reduce chromosomal number from diploid (2n or 46 in humans) to haploid (n or 23 chromosomes)
• Shuffling of genetic material to increase genetic variation

Question 5

Spermatogenesis

Answer 5

• Seminiferous tubules of testes -> prior to puberty, primordial germ cells undergo mitosis and line the tubules
• At onset of sexual maturity (testosterone-driven):
  1. Spermatogonia (2N) -> 1^o spermatocytes (2N); there can be TONS of mitosis here
  2. Meiosis I: division into 2^o spermatocytes (N); reduction step
  3. Meiosis II: division into spermatids (N); homologues separate
  4. Spermatid (N) to sperm (N) w/o further div
• ONGOING throughout life

Question 6

Mature sperm

Answer 6

• Capacitation: develop head and tail
  1. Shed all unnecessary baggage to become efficient swimmers, i.e., lose mitochondria
• Spermatogenesis takes 64 days
  1. Hundreds of mitotic divisions, and 200 million sperm per ejaculate

Question 7

45-y/o new dad and his 37-y/o wife gave birth to baby with achondroplastic dwarfism. Can we postulate a cause?

Answer 7

• Mitotic errors are common in sperm and the mutations accumulate in older dads and put offspring at risk
• New auto dominant mutation that likely came from the sperm

Question 8

What kinds of genetic risks might an AMA pregnancy pose for the child?

Answer 8

Risk of chromosome abnormalities, like trisomy 21

Question 9

Oogenesis

Answer 9

• Largely completed by birth: 30 mitoses
  1. 2.5 million oocytes at birth, but most degenerate (atresia) -> 400 mature to ova for repro age range
• Oogonia in F embryo begin Meiosis I in month 3 of embryologic prenatal development
  1. Meiosis I arrested in 1^o oocyte at diakenesis of prophase I by birth -> completed at ovulation
  2. Meiosis II is completed at fertilization
• Polar bodies inactive, and NOT fertilizable

Question 10

What happens in interphase before meiosis?

Answer 10

• DNA replication: each chromosome goes from univalent to a bivalent unit
• Identical sister chromatids joined by a centromere
• Diploid # of chromosomes (2N; 46)

Question 11

What are the stages of prophase I?

Answer 11

• Leptotene: chromosomes have already replicated, but lie on top of each other
• Zygotene: homologous pairs move together and pair or synapse
• Pachytene: first time you can see the bivalent chromosome (cheerleader pose) -> 2 homologous chromosomes now look like a tetrad
• Diplotene: crossing over occurs (KNOW THIS)
• Diakinesis: oogenesis frozen here until ovulation

Question 12

When does crossing over occur in prophase I?

Answer 12

Diplotene

Question 13

In what stage of prophase I is oogenesis arrested?

Answer 13

Diakinesis: until ovulation

Question 14

What is recombination? When does it occur? How often?

Answer 14

• Crossing over that occurs at chiasmata (areas of contact) during Diplotene (Prophase I)
• Occurs (on average) on one arm of each chromosome

Question 15

What is the purpose of crossing over?

Answer 15

• INC genetic variation
• Multiplies the already huge # of different gamete types produced by independent assortment

Question 16

What happens after prophase in meiosis I?

Answer 16

• Metaphase: nuclear membrane disappears, spindle appears, and pairs align on metaphase plate
• Anaphase: bivalents disjoin, and are pulled apart by spindles attached to chromosomal centromere
• Telophase and cytokinesis: chromosomes gather into nuclei and cell division occurs

Question 17

How is meiosis II different from meiosis I?

Answer 17

• Same steps, but much more rapidly
• Chromatids of same chromosome are pulled apart (going from N to N)
  1. NOT identical because crossing over occurred in Diplotene of Prophase or Meiosis I
• Occurs at fertilization in oogenesis

Question 18

38-y/o delivers a baby with down syndrome (trisomy 21). She is worried because she used cocaine during the pregnancy. What is the best response to her?

Answer 18

Trisomy 21 results from errors in meiosis I and no environmental issue puts the pregnancy at risk

Question 19

Woman has a child with an extra chromosome that is maternal. How can we tell which meiotic stage (1 or 2) that this nondisjunction resulted from?

Answer 19

• If all chromosome 21s are different DNA fingerprints, then its meiosis I
• 95% of maternal nondisjunction is meiosis I

Question 20

What is the key difference between mitosis and meiosis?

Answer 20

• The way chromosomes uniquely pair and align in meiosis

Question 21

How are the products of spermatogenesis and oogenesis different (image)?

Answer 21

Question 22

What cells/hormones determine male sex?

Answer 22

• 46 XY: SRY -> testes
  1. Leydig cell: testosterone -> converted to DHT, secondary sex characteristics
  2. Sertoli cells: AMH -> regression of mullerian ducts
  3. Mesonephric (Wolffian) ducts persist: epididymis, vas deferens, seminal vesicles

Question 23

What cells/hormones determine female sex?

Answer 23

• 46 XX: NO SRY -> ovary
  1. Granulosa cells: estrogen
  2. NO AMH -> mullerian ducts continue to evolve and mesonephric (wolffian) ducts regress

Question 24

What are the key hormones that determine the fate of the bipotential gonad?

Answer 24

• AMH: anti-mullerian hormone (MIS = mullerian inhibiting substance)
• Insl3 (insulin-like substance 3): may play a role in testicular descent (produced by the gonad)

Question 25

What are the key secondary sex characteristics at birth? Chief hormone?

Answer 25

- _Male_: mediated by DHT 1. Fusion of genital folds to form scrotal sac 2. Enlargement of genital tubercle -\> penis - _Female_: no testosterone or DHT 1. Genital folds become labia 2. Genital tubercle is the clitoris 3. Invagination of lower perineal body to form lower vagina 4. Mullerian ducts fuse to form upper vagina, cervix, uterus and Fallopian tubes - Further devo at puberty (via testosterone and estrogen)

Question 26

14-y/o presents with no breast development or periods. She is 46 XY, and has gonadal dysgenesis (did not differentiate): atrophic, streak gonads. What is true about her internal sex organs?

Answer 26

She has no sertoli cells and therefore no AMH. She has a uterus and tubes