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Development begins with fertilization.

Fertilization; The process by which the male gamete, (the sperm), &the female gamete,( the oocyte), unite to give rise a( zygote)

Second lecture Gametogenesis

are derived from germ cells that appear in the wall of the yolk sac at the 4th wk of development, from this location , these cells migrate by a meboid movement to the developing gonads where they arrive by the end of 5th wk

The chromosome theory of

It depends on specific genes that localized on the chromosomes of the father or the mother& inherited to the off sibling. Linked genes ; genes on the same chromosome tends to be inherited together.

Is the process where by one cell divides, giving rise to 2 daughter cells that are genetically identical to the parent cell, each daughter cell contain the total 46 chromosomes

There are 22 pairs of matching chromosomes, the (autosomes) ,& one pair of( sex chromosome.) if the sex pair is (XX )the individual is genetically female, if the pair is( XY)the individual is genetically male

diploid number of 46 chromosomes(at fertilization due to union of 2 gametes sperm &oocyte) haploid number of23 chromosomes(contain in each gamete)

Before a cell enters mitosis ,

It start(replication phase):
replicate it is DNA, at this phase: A- the chromosomes are extremely long B-diffusely spread through the nucleus. C- not recognized by light microscope

It is the 1st phase in mitosis

With the onset of mitosis the chromosome begins to coil, contract, & condense Each chromosome consists of 2 parallel subunits , chromatids joined at acentromer

At the prometaphase the chromatid become distinguishable.

during metaphase the chromosome line up in equatorial plane, &it is double structure is clearly visible, attached by microtubules extending from the centromere to the centriole, forming the mitotic spindle.


as the centromere of each chromosome divides followed by migration of chromatids to opposite poles of the spindle.


chromosomes uncoil &lengthen, the nuclear envelope reforms the cytoplasm

Cell division that take place in the germ cells to generate male & female gametes (sperm & egg)respectively It requier 2 cell divisions Meiosis 1 Meiosis 2 to reduce the number of the chr. To the haploid number of23.

1-Spermatocytes& primary oocytes will replicate their DNA ,so that each of the 46 chr is duplicated into sister chromatid . 2-the homologous chromosomes then align themselves in pairs, in process called synapsis 3- the paring is exact and point for point except for the XY combination. 4-these pairs will separate to 2 daughter cells Shortly after ---- meiosis 2 occur & separates sister chromatids. Each gamete then contain 23 chromosome

In meiosis 1

1-Critical event in meiosis 1 2-Is the interchange of chromatid segments between paired homologous chromosomes 3-It occurs during separation Chiasma: points of interchange are temporarily united and form an X-like structure 4- (30-40) crossovers(1-2 per chr.) with each meiotic 1 division are most frequent bet .genes that are far apart on chromosome


Results of meiotic divisions

1-genetic variability 2-each germ cell contains a haploid number of chromosomes so that( at fertilization) the diploid number of46 is restored

Polar bodies
During meiosis one primary oocyte gives rise to 4 daughter cells, each with 22 plus1 X chromosome Only 1 develops to mature gamete(the oocyte)the other3 (polar bodies)with little cytoplasm degenerate during subsequent development)

While 1 primary spermatocyte gives rise to 4 daughter cells 2 ( with 22 plus X chromosomes) 2 ( with22 plus Y chromosomes) All 4 will develop into mature gametes

Clinical correlates
Birth defects & spontaneous abortion:
Chromosomal & genetic factors

Chromosomal abnormalities:
1-numerical 2-structural It is estimated that 50% of conceptions end in spontaneous abortion 50% of these due to chromosomal abn. So25% of conceptuses have a major defects

Major birth defect

1-chromosomal abnormalities account of 7% 2-gene mutation account for additional 8% E.g. of chr . Abn.: 1-trisomy 16 2-triploidy 3-45,X(turner syndrome)

Numerical abnormalities
Normal human somatic cell contain 46 chr.(diploid)or2n Normal gamete contain23.haploid)or n Euploid: Refers to any exact multiple of n=diploid or triploid. Aneploid: Refers to any chr number that is not euploid Trisomy=extra chr is present Monosomy= 1 chr. Is missing

Structural abnormalities
meiosis Commonly )Nondisjunction) failure of separation of the paired chr. during meiotic division. Occur either in 1st or 2nd meiotic division mitosis occasionally (mitotic nondisjunction) =mosacisim i.e. some cells have normal & others are abnormal. in the embryonic cell during the earliest cell divisions . some cells have normal numbers of chr.23 & others have abnormal numbers same Affected individuals may exhibit few or many of the cch. Of a particular syndromes depending on the number of cells involved and their distribution.

As result one cell receive 22 chr, & the other 24 chr. In women the incidence increase with age especially at 35 yrs & older All have cch. Features known as syndromes

chromosomal abnormalities 2-translocations

Some times chromosomes break, &pieces of one chromosome attach to another. 2 types: 1-Balanced: breakage & reunion occur bet.2chr. But no critical genetic material is lost & individuals are normal. 2-unbalanced: In which part of the chromosome is lost & an altered phenotype is produced. E.g. unbalanced translocation bet. the long arm of chr 14& 21 during meiosis1 or 2 produce gametes with an extra copy of chr.21 one of the causes of Down syndrome

In which part of the chromosome is lost & an altered phenotype is produced. E.g. unbalanced translocation bet. the long arm of chr 14& 21 during meiosis1 or 2 produce gametes with an extra copy of chr.21 one of the causes of Down syndrome

Triosomy 21 down syndrome

Is usually caused by an extra copy of chr 21(triosomy21)
Features include:

Varying degrees of mental retardation

Craniofacial abnormalities include 1-upward slanting eyes 2- flat facies 3-small ears 4-cardiac defects 5-hypotonia They have high incidence of leukemia,infections,thyroid

dysfunction. Premature aging Nearly all develop signs of Alzheimer's disease after age 35

Causes of Down syndrome: 1-In 95% caused by trisomy 21 resulting

from meiotic nondisjunction,75% of these occurs during oocyte formation

Incidence of down syndrome is approximatly 1in 2000 conceptuses for women under age 25.Increase risk with age to1 in300 at age 35 % 1 in100 at age 40 2- In4% of cases there is an unbalanced translocation bet. Chr 21%chr 13,14,or15 3-The final1% are due to mosaicim resulting from mitotic nondisjunction

Klinefilter syndrome
Klinefilter : the cells have 47 chromosome & with

a sex chromosomal complement of the XXY type Sex chromatin body is found in 80% of cases The incidence is about 1 in 500 males Nondisjunction of the XX homologues is the most common causative event. Occasionally they have48 chr:44autosomess&4 sex chr(XXXY) although not feature the more Xchr there are, the more likely is some degree of mental impairment.

Turner syndrome
Female phenotype (general appearance) Gonadal dysgenesis Short stature Web neck Lymphedema of extremities Skeletal deformities Broad chest &widely spaced nipples

55% of these women. are monosomic for x chr.& chromatin negative due to non disjunction 80% of these women non disjunction of the male gamete is the cause In the remainder 20% it is either 1- due to structural abnormalities of the x chr. 2-mitotic non disjunction resulting in mosaicism is the cause

Structural abnormalities
Structural chromosome abnormalities Chromosomal breakage caused by environmental factors 1-viruses 2-radiation 3drugs

Results of chromosomal breakage

Partial deletion =p.d (loss piece of the chromosome)
eg,------(cri-du-chat) syndrome due to p.d of short arm of chr. 5 Catlike cry Microcephaly M.R CHD (congenital heart disease)

Angelman syndrome
Microdeletions: spanning only a few contiguous genes( microdeletion syndrome)or contiguous gene syndrome E.g. Microdeletion occur on the long arm of chr.15 Inheriting the deletion on the maternal chr. results in

Angelman syndrome

1. 2. 3. 4.

MR Cannot speak Poor motor development Prone to unprovoked&prologed periods of laughter

If the defect inherited on the paternal chr. Prader-willi syndrome is produced

Hypotonia MR Hypogonadism cryptorchidism

Regions of the chr that demonstrate a propensity to separate or break under certain cell manipulations E.g. Fragile x chromosome Cch features are: 1-MR 2-Large ears 3-Prominent jaw 4-Pale blue iris

Fragile site

Male affected more than female 2nd only to down syndrome as a cause of chromosomal MR

Gene mutation
change in the structure or function of single gene so called single gene mutation Equal to8% of all human malformation Dominant mutation :single allele is affected Recessive mutation :double alleles are affected Or the mutation is x-linked

All chromosomes have double alleles(dose of genetic determinants) Except x, y chromosomes

Diagnostic Techniques for identify in genetic Abnormalities

1-G- banding) Gimsa banding: Chromosomal preparation are treated with trypsin and stained with Gimsa to reveal patterns of light &dark bands that are unique for each chromosome. 2-fluorescence in situ hybridization(FISH): Uses specific DNA probes for identifying deletions of genetic material 3-fiber FISH more advanced

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