13. Urogenital system

endoderm at the cranial most part of the primitive gut. The arches are separated from each other by ectodermal clefts and form out pouching in the lateral wall of developing pharynx as endodermal pouches. The mesoderm which lies in the center of the arches form the arch arteries and musculature and the skeletal elements are formed from the neural crest cells, which migrate early from hindbrain region. The FGF signaling plays an important role in determining the migration and fate of neural crest cells in the arches, endodermal pouch formation and differentiation [7]. Though it was previously thought that the neural crest cells are important for pharyngeal arch development but nowadays it is shown that the endoderm of the pharyngeal apparatus acts as the principal organizer and thus it is proved that neural crest cells are not necessary for pharyngeal arch development. The out pocketing of the endoderm is significant for pharyngeal arch development and regulated by TBX1 and RA signaling [8]. The most well-known condition due to faulty development of third and fourth pouches is the DiGeorge syndrome which results due to submicroscopic chromosome deletion 22q11 and loss of approximately 30 genes. Treacher Collins is hypoplasia of the maxilla and mandible with coloboma of the lower eyelid, cleft palate, hearing impairment has an autosomal dominant inheritance affecting the first arch and results due to mutation in TCOF1 gene [1].

The cilia on the apical surface of the cells have an important role in human embryological development deciding cell specification, axis determination and pathology of human congenital disorders. A variety of congenital defects like polycystic kidney, laterality defects, nervous system defects, and retinal degeneration are associated with ciliopathies thus proving that cilia can serve as signaling factor in embryonic development. Cilia plays an important role in Hedgehog patch smoothened Gli pathway and thus it regulates the Gli protein activity. The cilia transition zone a short segment just above the basal body acts as an essential gatekeeper for movement of protein in and out of the cilia. Cilia also play an important role in movement of fluid in various confined embryonic spaces, which may act as a developmental shear force [9]. The congenital polycystic kidney disease, which results in numerous cyst formations, can be inherited as autosomal dominant or recessive. In autosomal recessive type the cysts are formed in the collecting tubules and it is a progressive disorder though less common but highly progressive and leads to kidney failure early in infancy and childhood. The autosomal dominant type is more common (1/500 to 1/1000) results in cyst formation in all segments of the nephron is less progressive and does not result in renal failure till adulthood, The above two types of conditions are related to the mutation of genes that code ciliary protein and thus fall under the group of disorders the ciliopathies which are creating a lot of interest in recent times. Bardet-Biedl syndrome and Meckel-Gruber syndrome are characterized with renal

cysts and other features are also some of the ciliopathies recently identified [2].

Organogenesis results due to reciprocal interaction between the differentiated epithelial cells and the underlying mesenchyme, which is brought about by signaling molecules. The

11. Ciliary development

86 Genetic Diversity and Disease Susceptibility

12. Reciprocal interactions

The urogenital system develops from a common mesodermal ridge, i.e., the intermediate mesoderm. The intermediate mesoderm gives rise to three overlapping kidney systems the pronephros, the mesonephros and the metanephros. The metanephros, which appears by fifth week, gives rise to the definitive kidney in humans. The mesonephric duct of the intermediate mesoderm gives rise to an ureteric bud which forms the collecting part of the kidneys the renal pelvis, calyces, 1–3 million collecting tubules. The interaction of this ureteric bud from the mesonephric duct with the mesenchyme of the metanephric blastema is the key factor in determining the initiation of kidney development. WT1 is the transcription factor expressed by the mesenchyme of metanephros, which increases the sensitivity of the metanephros to interact with the ureteric bud and respond to it. The branching and growth of ureteric bud is under control of production of Glial derived neurotrophic factor (GDNF) and Hepatocyte growth factor produced by the mesenchyme of metanephros which bind to the receptor on ureteric bud. The ureteric bud too produces FGF and BMP7, which induce the metanephric mesenchyme to undergo proliferation, and also blocks apoptosis. Epithelial conversion of the mesenchyme of metanephros occurs under the influence of WNT9B and WNT6 from the ureteric buds, which in turn activate PAX2 and WNT4 in the metanephric mesenchyme. All these interactions lead to the modifications in extracellular matrix protein to form the characteristic epithelial basal lamina rich in laminin and type IV collagen. Wilms tumor, a malignant neoplasm of the kidney usually affecting children of age group 5–10 years, is due to mutations inWT1 gene on chromosome 11p13 and can be associated with other abnormalities. Mutations in GDNF gene, which causes branching of the ureteric bud and interaction of the ureteric bud and metanephros, can result in renal agenesis [2].

cell division this inactive X chromosome is late replicating. But not all of the X chromosome is inactivated. Genes at tip of Xp (short arm) and other genes at other loci of Xp also escape deactivation. There are more genes which get deactivated in Xq thus resulting in less severe phenotypic effects in people with Xq deletions compared to Xp deletions. In men and women with more than one X chromosomes the number of Barr bodies seen during interphase is one less than the total number of X chromosomes. Dosage compensation mechanisms are evolved which lead to a balance in X linked gene products between sexes. This can be achieved by two fold increase in expression of X linked genes in males, a two fold down regulation of X linked genes in females and lastly complete inactivation of one of the two X chromosomes in females.

Developmental Genetics and Preimplantation Genetic Diagnosis

http://dx.doi.org/10.5772/intechopen.77965

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The mechanism of birth defects can be broadly grouped as deformation, disruption, dysplasia and malformation. Major congenital anomalies are those that are life threatening but minor abnormalities are those that do not pose a threat to extra uterine survival. Examples of structural anomalies are cleft lip and palate, diaphragmatic hernia, hydrops, congenital heart

In the first trimester, nuchal translucency is a marker of chromosomal anomalies. In the second trimester there may be echogenic bowel, echogenic chordae or absent nasal bone. Presence of these biophysical markers in early ultrasound becomes an indication to test for chromosomal anomalies in the fetus. Chromosomal anomalies can be detected by performing direct tests (fetal blood sampling, amniocentesis, cordocentesis) on the fetus or chorionic villi (chorionic villus sampling). Indirect screening tests can be done in mother (fetal DNA in maternal serum)

There are about 25–30 trillion cells (1 trillion = 1,000,000,000 000) in the human body. They are of two types: somatic cells and gametes. The somatic cells are diploid with 23 pairs of chromo-

Each chromosome has 100–1000 genes. The genetic information contained in Chromosomes is in the form of base pairs. The total base pairs in a haploid set of 23 chromosomes are around 3000 million. Direct testing can be karyotype, FISH or QF PCR, Micro deletion detection, microarray, mutation specific testing or exon sequencing. Single nucleotide polymorphism

A complex of above mentioned strategies are adapted in mammals [10].

16. Pathogenetic mechanisms of birth defects

some. The gametes are haploid with 23 chromosomes [11].

diseases, choroid plexus cysts and short femur.

17. Markers of structural anomalies

to obtain indirect evidence.

18. Genetic testing

testing is also important [12–14].

#### 14. Molar pregnancy

Hydatiform mole can be either partial or complete in which the placenta may proliferate abnormally. This can be partial with 69 chromosomes or triploid in which 46 chromosomes are derived from father and 23 from mother, which can be either due to dispermy or endoduplication of haploid sperm. In complete hydatiform molar pregnancy there are only 46 chromosomes and solely paternal in origin. It's due to fertilization of an empty ovum by two sperms or duplication of single sperm. The complete mole can undergo malignant change into invasive choriocarcinoma and outcome can be fatal if untreated [1, 3].

#### 15. Multifetal gestation

Multiple births result from simultaneous nurturing two or more embryos in the uterus and can be of monozygotic or dizygotic types. In monozygotic twins a very early division of the zygote before separation of the cells which form chorion result in dichorionic twins, twinning at blastocyst stage results in monochorionic diamniotic twins which constitutes about 70% of monozygotic twins. Twining after first week leads to monoamniotic twins. There is 2–5 times increase in monozygotic twins in babies born by IVF. Very late divisions after 14 days can lead to conjoined twins which is common in females about 75% and thus late twinning and X inactivation can be interrelated. Dizygotic twins result from fertilization of two ova by two sperms thus they are also called fraternal twins. Dizygotic twins are diamniotic and dichorionic. Increased maternal age, family history and intake of ovulation inducing drugs can increase risks for dizygotic twins [1, 3].

In 1961 Dr. Mary Lyon experiments on mice led to the development of Lyon's hypothesis regarding X chromosome deactivation. Later this was recognized and the term lyonization is used for the process of X chromosome, which occurs around 15th, or 16th day of development in female embryos. Either the maternal or paternal X chromosomes can be deactivated in any particular cell and thereafter the same X chromosome is inactivated in daughter cells. Barr bodies are the inactivated darkly stained mass of chromatin seen during interphase. During cell division this inactive X chromosome is late replicating. But not all of the X chromosome is inactivated. Genes at tip of Xp (short arm) and other genes at other loci of Xp also escape deactivation. There are more genes which get deactivated in Xq thus resulting in less severe phenotypic effects in people with Xq deletions compared to Xp deletions. In men and women with more than one X chromosomes the number of Barr bodies seen during interphase is one less than the total number of X chromosomes. Dosage compensation mechanisms are evolved which lead to a balance in X linked gene products between sexes. This can be achieved by two fold increase in expression of X linked genes in males, a two fold down regulation of X linked genes in females and lastly complete inactivation of one of the two X chromosomes in females. A complex of above mentioned strategies are adapted in mammals [10].
