17. Markers of structural anomalies

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) to obtain indirect evidence.

## 18. Genetic testing

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

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

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

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

into invasive choriocarcinoma and outcome can be fatal if untreated [1, 3].

and metanephros, can result in renal agenesis [2].

14. Molar pregnancy

88 Genetic Diversity and Disease Susceptibility

15. Multifetal gestation

can increase risks for dizygotic twins [1, 3].

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

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 testing is also important [12–14].

#### 19. Karyotyping

Karyotyping detects the number of chromosomes (Aneuploidies or the gross structure of chromosomes). A karyotype detects any chromosomal anomaly greater than 5 Million base pairs. This could be monosomy, trisomy, tri and tetra ploidy, deletions, duplications, etc. Karyotyping is done by culture that may take 3–4 weeks. An example is detection of Down's syndrome by karyotyping of fetal cells obtained after amniocentesis). Any abnormality lesser than 5000 million base pairs cannot be detected by karyotyping. For example a small micro deletion or a mutation responsible for a genetic disease like CAH (Congenital genital hyperplasia) or spinal muscular atrophy.

An analogy is a library with 23 bookshelves. Each shelf has 10 rows and each row has 25 books. A karyotype is to find if a bookshelf is in excess or missing. Also it can also tell if a major part of bookshelf is broken. A micro deletion is like a missing row in a bookshelf.

Developmental Genetics and Preimplantation Genetic Diagnosis

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A microarray can identify if a book or two is missing in the library but then sometimes it tells a book which is not important. A mutation specific test is like checking if a particular book is

An Exom sequencing is like checking if a few pages are missing in any book in any shelf of the whole library. Genome sequencing is like checking if any paragraph or sentence is missing in any book in any shelf in the whole library. Majority of the fetal birth defects are due to single

Preimplantation genetic testing is defined as a procedure to remove one or more nuclei from oocytes (polar bodies) or embryos for genetic testing before transfer [15, 16]. Preimplantation genetic diagnosis PGD is a term used to determine whether a certain mutation or an unbalanced chromosomal complement has been transmitted to the oocyte or embryo when one or both genetic parents carry a genetic mutation or a balanced chromosomal rearrangement. Preimplantation genetic diagnosis is done to avoid transfer of embryos with mutation and

Preimplantation genetic screening is term used when both genetic parents are chromosomally normal and their embryos are screened for any genetic defects before implantation to improve

In preimplantation genetic screening and 24 chromosome copy number analysis (CGH, array comparative genomic hybridization, real-time quantitative PCR, SNP microarray) the aim is

Figure 10. (a) Diagrammatic illustration of the method for polar body biopsy. (b) Blastomere biopsy. (c) Multiple cell

missing. For example a book on Indian cooking in a row of cookery books.

gene/multiple gene mutations and cannot be identified in karyotyping.

23. Preimplantation genetic testing

identify healthy embryos for transfer [17].

the success rate of embryo transfer [18, 19].

biopsies from blastocyst.
