Prefertilization events Prefertilization events • Sexual reproduction• -occurs when female &

male gametes unite at fertilization

• A. Gametes• -PGC from wall of the

yolk sac at week 4 migrate into future gonad region

• - are produced by gametogenesis (oogenesis in the female and spermatogenesis in the male)

Chromosomes Chromosomes

• Single & duplicate

• Normal somatic cells & PGC;

• -46 single and 2N amount of DNA or 23 homologous pairs or diploid

• - pairs 1 to 22 are autosomal (non-sex) pairs

• -pair 23 consists of the sex chromosomes (XX for a female XY for a male)

• Gamates;• -contain 23 single chromosomes or

haploid (22 autosomes and 1 sex chromosome) and 1N amount of DNA

• -female gametes contain only the X sex chromosome

• -male gametes contain either the X or Y sex chromosome: male gamete determines the genetic sex

• Meiosis1• -DNA

replication• -synapsis• -crossover• -alignment• -disjunction• -cell

division• Meiosis2 • -alignment• -disjunction• -cell

division

Human birth defects Human birth defects

• Enviromental or genetic factors

• Agents that cause congenital malformation is teratogens

• About 3% liveborn infants have defects at birth this statistic doubles by the end of the first postnatal year

• Approximately 20% of infant deaths in the USA result from birth defect

Numerical chromosomal abnormalitiesNumerical chromosomal abnormalities

• If one additional chromosome is present, the condition is called trisomy

• If one chromosome is absent, the condition is called monosomy

• Trisomy and monosomy are most often caused by meiotic nondisjunction of chromosom

Autosomal abnormalitiesAutosomal abnormalities

• Trisomy 21 (Down syndrome)• -Mother under 25 is 1:2000• -mother 35 is 1:300• -mother 40 is 1:100• -mother over 45 is 1:25• -May affect all parts of the brain;

mental retardation, microcephaly, microphthalmia, colobomata, cataracts, glaucoma

• -epicanthic folds, simian crease, congenital heart defects, umbilical hernia & duodenal atresia

• Alzheimer neurofibrillary tangeles and plaques found in the brains of persons over 35 years

Trisomy 18 (Edwards` syndrome)Trisomy 18 (Edwards` syndrome)

• Incidence is 1:5000• Infants usually die

soon after birth (2 months)

• Mental retardation, congenital heart defects, prominent occiput, low-set ears, micrognathia, flexed digits

Trisomy 13 (Patau syndrome)Trisomy 13 (Patau syndrome)

• Is much less common than 21

• Incidence is 1:20000• Infants usually die soon

after birth (3 months)• Mental retardation,

microphthalmia, congenital heart defects, deafness, colobomata, cleft lip and cleft palate

Sex chromosome abnormalitiesSex chromosome abnormalitiesklinefelters syndrome (47 XXY)klinefelters syndrome (47 XXY)

• Is found only male with an incidence 1:500 male births

• Male hypogonadism, sterility & gynecomastia

• Some persons with this syndrome have 48 chromosomes (44 autosomes & 4 sex chromosome 48 XXXY

Turner syndrome (45 XO)Turner syndrome (45 XO)

• Is found only in females, with an incidence of 1:5000 live female births

• Female hypogonadism (gonadal dysgenesis)

• Sex chromatin negative• Infantile genitalia,

hypoplastic ovaries, congenital heart defect, webbed neck, lymphedema of the extermities

Triple X syndromeTriple X syndrome

• Has an incidence of 1:960 births

• Presence of two sex chromatine bodies (Barr bodies)

• Usually fertile & 20% are mildly mentally retarded

• Santhi Soundarajan

Structural abnormalitiesStructural abnormalitiescri-du-chat syndromecri-du-chat syndrome

• Results from deletion of the short arm of chromosome 5

• Has an incidence of 1:100000 births

• Mental retardation, microcephaly, congenital heart defects, and a cat like cry

Contiguous gene syndromeContiguous gene syndrome

• Angelman syndrome;• -is associated with

deletion of band q12 on chromosom15 (found in the mother)

• -mental retardation, sezures, and dystaxia

• Prader-willi syndrome• - is associated with

deletion of band q12 on chromosom15 (found in the father)

• - mental retardation, hyperphagia, and hypogonadism

Gene mutationGene mutation

• Genes exits as pairs, or alleles (exception of the X & Y chromosomes in the male).

• If a mutant gene gene produces an abnormality in a single dose, despite the presence of a normal allele, it is a dominant mutation.

• If both alleles must be abnormal (double dose) or if the mutation is X-linked in the male, it is a recessive mutation.

Diagnostic techniques for Diagnostic techniques for identifying genetic abnormalitisidentifying genetic abnormalitis

• Cytogenetic analysis• High resolution

metaphase banding techniques

• Fluorescence in situ hybridization (FISH)

• Spectoral karyotype analysis (SKY)

Oogenesis Oogenesis

• PGC; arrived in gonad at week 4, differentiate into oogonia , then mitotic division , differentiate into primary oocytes

• All primary oocytes are formed by fifth month of fetal life; no oogonia are present at birth

• primary oocytes remain dormant in prophase of meiosis1 from fifth month of fetal life at least until puberty (about age 12), after puberty 15 to 20 primary oocyte will begin maturation with each ovarian cycle, with usually only one reaching full maturity in each cycle.

• After puberty, a primary oocyte completes meiosis1 to form two daughter cells: the secondary oocyte and the first polar body

• The secondary oocyte enters meiosis2 when the chromosomes align at the metaphase plate, ovulation occures. After this point, oogenesis is complated outside the ovary, in the uterine tube where fertilization usually occures

• The secondary oocyte remains arrested in metaphase of meiosis2 until fertilization occurs

• At fertilization, the secondary oocyte will complete meiosis2 to form a mature oocyte and a second polar body

• Approximate number of oocytees;• -primary oocytes; 7 million at 5 months• 2 million at birth• 400000 at pubert• -secondary oocytes; 12 ovulate per year• up to 480 reproductive • -reduced; birth control pills, women

pregnant

Oogenesis & Spermatogenesis Oogenesis & Spermatogenesis

• PGC; arrive in gonad at week 4, remain dormant until puberty

• At puberty; differentiate into spermatogonia• Spermatogenesis• spermiogenesis