sex chromosome

Question 1

Y chromosome
– ~____ genes
• X chromosome
– >____ genes

Answer 1

200

1000

Question 2

The X chromosome

Answer 2

Only ONE copy of the majority of genes on the X chromosome is necessary for normal function
– Two copies of some of the genes may actually be detrimental
– In somatic cells of females (not males), one copy of the X chromosome randomly turned off
• “Random X inactivation”

Question 3

X Chromosome Inactivation • Occurs during the ______

Answer 3

X Chromosome Inactivation • Occurs during the 1st week of embryogenesis

Question 4

Females are functionally _______

Answer 4

Females are functionally mosaic for their X chromosomes

Question 5

XIST – gene

Answer 5

XIST – gene located on the X chromosome
• Expressed only from the inactive X
• X inactivation can’t occur in it’s absence
• Unclear mode of action

Question 6

Nonrandom X chromosome inactivation

Answer 6

– Occurs when there is a structurally abnormal X chromosome

• more of the normal Xs are turned on

Question 7

Skewed X inactivation

Answer 7

Skewed X inactivation
– Observed when a female shows signs or symptoms of an X-linked recessive condition, such as Duchene Muscular Dystrophy or Fragile X Syndrome
– Instead of a random inactivation pattern more of the X chromosome with normal gene is turned off

Question 8

Turner Syndrome

Answer 8

45,XO
• Signs at birth
– Prenatal cystic hygroma
– Webbed neck
– Puffy hands & feet
– Heart defects like coarctation of the aorta
• Short stature
• Normal intelligence
• Infertility due to non-functioning ovaries
• Hormone dysfunction
• Distinctive traits such as low set ears, broad chest • Occurs in 1/2,500 newborn girls

Question 9

Kleinfelter Syndrome

Answer 9

47, XXY
•  Can be seen in childhood
–  Learning disabilities
–  Delayed speech and language –  Tendency towards being quiet
•  Tall stature
•  Small testes
•  Reduced facial and body hair
•  Infertility
•  Hypospadias
•  Gynecomastia
•  Occurs in 1/500 – 1/1000 newborn boys

Question 10

Jacobs Syndrome

Answer 10

47,XYY 
•  Learning disabilities
•  Speech delays
•  Developmental delays
•  Behavioral and emotional difficulties 
•  Autism spectrum disorders
•  Tall stature
•  Occurs in 1/1000 newborn boys

Question 11

Triple X Syndrome

Answer 11

47,XXX
– May have tall stature
– Increased risk of
•  Learning disabilities
•  Delayed speech
•  Delayed motor milestones •  Seizures
•  Kidney Abnormalities
– Occurs in 1/1000 newborn girls

Question 12

Gonad Determination is _______

Answer 12

Chromosomal

Question 13

Secondary Sex Determination

Answer 13

– Gonadal development then determines secondary sex characteristics
• Includes sex-specific organs
– Penis, seminal vesicles & prostate gland
– Vagina, cervix, uterus, fallopian tubes & mammary glands
• Includes other phenotypic features – Body habitus & musculature
– Hair growth
– Vocal Cartilage

Question 14

4th week of conception

Answer 14

– Primordial germ cells form in wall of

yolk sac

Question 15

5th week of conception

Answer 15

– Coelomic epithelium becomes genital ridge

Question 16

6th week of conception

Answer 16

– Primordial germ cells migrate to the dorsal mesentary of the hindgut and enter the undifferentiated gonad
– Epithelial cells of gonadal ridge proliferate and form primitive sex cords

Question 17

7th week of conception

Answer 17

7th week of conception
– Differentiation of genital ridge into • Sertoli cells - eventually produce
sperm
• Leydig cells – interstitial cells

Question 18

8th week of conception

Answer 18

– Leydig cells begin producing testosterone
– Sertoli cells begin producing Anti-Mullerian Hormone (AMH)
– Primitive sex cords differentiate into
• Testis cords & rete testis, eventually to become seminipherous
tubules during puberty

Question 19

– SF1/NR5A1

• Stimulates

Answer 19

– SF1/NR5A1

• Stimulates differentiation of the Sertoli & Leydic cells

Question 20

WNT4 protein

Answer 20

Extracellular signaling factor responsible for differentiation of
the ovary
• Inhibited by SOX9

Question 21

DHH gene

Answer 21

A nuclear hormone receptor

• Up-regulated by WNT4 • Downregulates SOX9

Question 22

RSPO1 gene

Answer 22

• Coactivator of the WNT pathway

Question 23

Sexual dimorphism:

On this 1st day of life

Answer 23

– Obtain FISH studies for Sex Chromosomes and a Karyotype (or Chromosomal Microarray)
– Order hormone studies
• LH, FSH, Testosterone, Dihydrotestosterone, +/-
AMH
– Consider ultrasound study
• Evaluate for gonads & uterus – Surgical consult with Urology

Question 24

Androgen Insensitivity Syndrome (AIS)

Answer 24

46, XY
– X-linked gene, AR
– Mutation causes abnormality of the androgen
receptor
• Even though the body makes androgens (testosterone), it doesn’t necessarily recognize or respond to it
• Phenotypes range from mild under-virilization (Partial AIS) to full sex reversal (Complete AIS)
– Previously called “Testicular feminization”

Question 25

5-Alpha Reductase Deficiency –

Answer 25

46, XY
– X-linked gene, AR
– Mutation causes decreased ability of the body
to convert testosterone to dihydrotestosterone
– Phenotype shows undervirilized male with increased virilization at the time of puberty

Question 26

Disorders associated with the SRY gene

Answer 26

– 46, XY or 46, XX
– Y-linked gene
– Deletion or absence of the gene results in full 46, XY sex reversal and a phenotypically normal female
– Ectopic presence of the SRY gene in a 46, XX individual results in a phenotypically normal male
– Mutations in the SRY gene in a 46, XY individual results in decreased or absent production of Anti Mullerian hormone & under virilization of a male

Question 27

Denys-Drash & Frasier Syndrome

Answer 27

– Sex reversal with 46, XY
– Due to mutations in the WT1 gene
– Both cause different types of chronic kidney disease
• Diffuse mesangial sclerosis
• Focal segmental glomerulosclerosis
– Increased risk for Wilms Tumor
– WT1 – transcription factor for SRY gene

Question 28

Congenital Adrenal Hyperplasia –

Answer 28

Ambiguous genitalia in 46, XX – 21-hydroxylase deficiency
– Complicated by salt wasting in the first few weeks of life and with times of metabolic stress
• Decreased sodium and chloride • Increased potassium