genetic determination of the sex marie Černá lecture no 504-v
TRANSCRIPT
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Genetic determination of the sex
Marie Černá
Lecture No 504-V
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Meiosis – reconstruction of genetic material
• Rearrangement of chromosomes on the basis of crossing-over
• Chance segregation of maternal and paternal chromosomes into gametes
– combination number 223 (8 388 608)
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Meiosis
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Prophase of Meiosis I
1. Leptotene – chromosome condensation
2. Zygotene – chromosome synapse → bivalent
3. Pachytene – chromatid tetrad, crossing-over
4. Diplotene – chiasmata
5. Diakinesis – chromosome segregation
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Gamete maturation
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Male meiosis - spermatogenesis
• is initiated during puberty by androgens• takes about 64 days• includes spermiogenesis
conversion of spermatids into functional spermatozoa:
- formation of the acrosome
- nucleus condensation and cytoplasm shedding
- formation of the neck, midpiece and tail
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Female meiosis - oogenesis
• dictyotene state – in the fetus at 12 – 20 weeksdivision of the primary oocytes stops
at diplotene of prophase of Meiosis I• ovulation - from puberty to menopause
the secondary oocyte is shed into the uterine tube →division of the secondary oocytes stops
at metaphase of Meiosis II • fertilization - entry of a sperm the ovum
the end of Meiosis II
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Spermatogenesis Oogenesis
spermatogonia↓
primary spermatocytes↓
secondary spermatocytes↓
spermatids↓
spermatozoa
oogonia↓
primary oocytes↓
secondary oocytes↓
fertilized egg (zygote)
mitosis
meiosis I
meiosis II
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Barr body
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Sex determination
• in mammals (humans),
some insects (fruit flies)
• in some insects
(grasshoppers, crickets, roaches)
• in birds, some fishes,
some insects (butterflies, moths)
• in bees and ants
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The sex is estimated:
• Genetic determination →
GONADS → hormones
• Hormonal differentiation →
genital ducts, external genital + brain
• Psychological differentiation →
self-determination
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Early developmentpaired indifferent gonad
• in the 5th week of pregnancy• up to 2 000 primordial germ cells from
the endoderm of the yolk sac infiltrate
the primitive sex cords within
the mesodermal genital ridges, which are developments of the coelomic epithelium
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Further development without presence of the Y chromosome
• the primitive sex cords break down• proliferation of the epithelial cortical cords• oestrogens, from the maternal system,
placenta and fetal ovaries, →the paramesonephric Műllerian ducts develop
→ the uterine tubes and uterusthe mesonephric Wolffian ducts regressdifferentiation of the external genitalia
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The SRY gene on the Y chromosome• in the 7th week „zinc finger protein“ is activated• leads to proliferation in the testis cords:
- Leydig cells from mesenchyme →androgens (testosterone) →the mesonephric Wolffian ducts develop
→ vas deferens and epididymis- Sertoli cells from epithelium, in the 4th month
→ Műllerian inhibiting substance (MIS) → the paramesonephric Műllerian ducts regress
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The SRY gene on the Y chromosome
• production of androgens (testosterone) →• in the 8th – 18th week (until the 4th month)
differentiation of the external genitalia
testosterone under action of local 5-α-reductase
converts to dihydrotestosterone• in the 7th month of pregnancy
contraction of the gubernaculum
– descent of the testis into the scrotum
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Puberty is triggered by
hormones secreted by the pituitary gland:
• Adrenal glands → androgens (androsterone) →
pubic and axillary hair in girls
• Ovaries → oestrogens → breast growth,
menstruation, uterus matur., pelvis broadening
• Testes → enlargement of the testes
→ androgens (testosterone) →
penis and larynx growth, spermatogenesis
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Traits Sex-limited Sex-influenced
expressed in only one sex -
secondary sexual characteristics
level of their expression is different in different sex - early baldness
as an autosomal dominant trait in men
both are encoded by genes on autosomes
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Turner syndrome
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Turner syndrome
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Turner syndrome
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Klinefelter syndrome
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Klinefelter syndrome
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Klinefelter syndrome
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Chromosome Y
• Pseudoautosomal homologous regions at the distal ends of short (Xp and Yp) and long (Xq and Yq) arms of sex chromosomes → homologous recombination in meiosis I
• SRY gene on short arm Yp,
determines male sex (gonads - testes)
• AZF regions on long arm Yq, determine
development of male gametes (sperms)
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Disorders of Sex Determinationdue to Mutation of SRY Gene
Male phenotype with karyotype 46,XX can be caused by abnormal presence of SRY gene:
• SRY gene is transferred to X chromosome during abnormal crossing-over out of homologous regions of X and Y chromosomes
• SRY gene is transferred to autosome by translocation
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Disorders of Sex Determinationdue to Mutation of SRY Gene
Female phenotype with karyotype 46,XY can be caused by missing of SRY gene:
• SRY gene is deleted
• SRY gene is mutated
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Disorders of Gonadal and Sexual Development
• hermaphroditism – presence of
both ovarian and testicular tissue
→ the genitalia are ambiguous• pseudohermaphroditism – presence of
gonadal tissue of only one sex
but with ambiguous or opposite
external genitalia
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Female pseudohermaphroditism
46,XX karyotypes → normal ovaries, but
male external genitalia
Congenital adrenal hyperplasia
- autosomal recessive disorder
- deficiency of 21-hydroxylase
of the adrenal cortex
- ↓ cortisol + aldosteron, ↑ androgens
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Congenital adrenal hyperplasia
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Male pseudohermaphroditism
46,XY karyotypes → normal testes, but
female external genitalia
Deficiency of the steroid 5-α-reductase
- autosomal recessive disorder
Androgen insensitivity syndrome
- X-linked syndrome of testicular feminization
- mutations of the androgen receptor gene
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DNA is the most stable molecule of our body
secret room in the tomb of Amenhotepa II
in Kings’ valley in Luxor
queen Nefertiti
1381 – 1344 B.C.
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LiteratureGenetics in Medicine, sixth edition, revised reprintThompson & ThompsonSaunders, 2004
Chapter 2: Chromosomal Basis of HeredityHuman Gametogenesis and Fertilizationpages 12 – 16
Chapter 10: Clinical CytogeneticsThe Sex Chromosomes and Their Abnormalitiespages 165 – 179
Clinical Case Studies: 27, 32
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Literature
Medical Genetics at a Glance, second edition,Dorian J. Pritchard & Bruce R. KorfBlackwell Publishing, 2008
Part 1: Developmental biology 10,(11,12),13Part 2: Medical genetics 23, 25pages 28 – 35, 59 – 61, 64 – 65