sex chromosome Flashcards
Y chromosome
– ~____ genes
• X chromosome
– >____ genes
200
1000
The X chromosome
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”
X Chromosome Inactivation • Occurs during the ______
X Chromosome Inactivation • Occurs during the 1st week of embryogenesis
Females are functionally _______
Females are functionally mosaic for their X chromosomes
XIST – gene
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
Nonrandom X chromosome inactivation
– Occurs when there is a structurally abnormal X chromosome
• more of the normal Xs are turned on
Skewed X inactivation
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
Turner Syndrome
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
Kleinfelter Syndrome
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
Jacobs Syndrome
47,XYY • Learning disabilities • Speech delays • Developmental delays • Behavioral and emotional difficulties • Autism spectrum disorders • Tall stature • Occurs in 1/1000 newborn boys
Triple X Syndrome
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
Gonad Determination is _______
Chromosomal
Secondary Sex Determination
– 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
4th week of conception
– Primordial germ cells form in wall of
yolk sac
5th week of conception
– Coelomic epithelium becomes genital ridge
6th week of conception
– 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
7th week of conception
7th week of conception
– Differentiation of genital ridge into • Sertoli cells - eventually produce
sperm
• Leydig cells – interstitial cells
8th week of conception
– 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
– SF1/NR5A1
• Stimulates
– SF1/NR5A1
• Stimulates differentiation of the Sertoli & Leydic cells
WNT4 protein
Extracellular signaling factor responsible for differentiation of
the ovary
• Inhibited by SOX9
DHH gene
A nuclear hormone receptor
• Up-regulated by WNT4 • Downregulates SOX9
RSPO1 gene
• Coactivator of the WNT pathway
Sexual dimorphism:
On this 1st day of life
– 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
Androgen Insensitivity Syndrome (AIS)
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”
5-Alpha Reductase Deficiency –
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
Disorders associated with the SRY gene
– 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
Denys-Drash & Frasier Syndrome
– 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
Congenital Adrenal Hyperplasia –
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
