This document discusses various topics related to genetics and DNA analysis including: 1. Scientists are using DNA sequencing to study rare genetic diseases, human origins, and microbes in our bodies. Understanding genome algorithms is key to understanding their applications and limitations. 2. Prenatal screening tests like nuchal translucency measurement and blood tests can detect risks for conditions like Down syndrome. Invasive tests provide confirmation but carry higher risks of complications. 3. Genetic counseling analyzes family trees and inheritance patterns to determine risks of transmitting genetic diseases to offspring.

1. DNA,Genetics and
Hardware
By : Vishwas Narayan

2. Why study this ?
● scientists are using sequencing to study rare genetic diseases in children.So
sequence the genomes of ancient humans to learn more about human origins
and evolution and patterns of migration
● They're using it to study the vast number of microbes, bacteria and such that
live inside our bodies, especially in our guts, and help us do things like digest
food.Or to simply study the basic ways in which genomes work.To answer
basic questions, like what does all the DNA and the genome do?How does
the genome work?
● First of all, understanding these algorithms is key to understanding
where they will succeed and where they'll fail novo shotgun assembly
problem

3. continued...
● Nuchal translucency measurement, PAPP-A, free or total beta- hCG: this is processed through
sonography to visualize the increased thickness of subcutaneous fluid at NT. The amount of fluid at the
posterior aspect of the fetal neck is called nuchal translucency (NT) and can be measured on
ultrasonography as early as the 6th week of gestation. Increased NT has been found to be associated
with trisomies and congenital cardiac defects. NT combined with levels of free hCG and pregnancy-
associated plasma protein A (PAPP-A) is used to screen for Down’s syndrome in the first trimester with
their combined detection rate being around 80 %.
● Ultrasonography and fetal echocardiography can be offered to pregnant women if fetal NT is found
to be at least 3.5 mm (and aneuploidy screen is negative and no chromosomal abnormalities have been
detected) as there is still a high risk of congenital cardiac/abdominal wall defects and other genetic
syndromes. It can detect the risk of Down syndrome and is recommended in 11 to 14 weeks of
pregnancy.
● This is a new genetic test which analyzes the DNA of the fetus from a sample of the maternal
blood. It can be performed anytime after the 9th week of gestation up to the 22nd week. A positive test
is indicative of birth defects and further invasive tests may be warranted to confirm the diagnosis.

11. continued...
● NIPS helps to detect trisomies like Down syndrome, trisomy 14 and 18, cystic fibrosis, hemophilia,
etc. It can also reveal the gender of the fetus. The test has higher sensitivity compared to nuchal
translucency as well as first-trimester screening tests and quad test. Currently, the American College of
Obstetricians and Gynecologists Committee on Genetics recommends NIPS for high –risk women with
● Invasive tests include chorionic villus sampling (CVS), amniocentesis and fetal blood sampling (FBS).
These tests are associated with an elevated risk of complications, e.g., limb injuries have been
reported after CVS; miscarriages have been reported after amniocentesis and FBS.
● While CVS is ideally performed between the 8th to 10th week of gestation, amniocentesis is performed
in the second trimester between the 16th to the 20th gestational weeks. It cannot be performed earlier
due to the risk of talipes and fetal loss. Similarly, FBS is not performed as often due to the associated
high risk of miscarriages.

12. Second-trimester screening tests
● Triple markers [human chorionic gonadotropin (hCG), unconjugated estriol, and maternal alpha-
fetoprotein levels] can detect Down’s syndrome in 70 % of the cases.
● Quadruple markers [human chorionic gonadotropin (hCG), unconjugated estriol, maternal alpha-
fetoprotein levels, and inhibin A levels] can detect Down’s syndrome in approximately 80 % of the
cases.
● The high value of alpha-fetoprotein level in the blood determines the high risk of neural tube defect of
the brain and spinal cord, birth defects of the abdominal wall and complications in late pregnancy such
as, slow growth, miscarriage or death of the fetus.
● A blood test is followed by ultrasonography and amniocentesis for confirmation of diagnosis and double
checking of the result of blood tests.

13. Genetic Counseling
Genetic counseling is the process by which a trained health care provider determines the risk of parents
transmitting a genetic disease to their unborn fetus. During this arduous process, the family trees of
prospective parents are investigated in detail, analyzed inheritance patterns, and the potential for
transmission of the affected genetic trait.
● Prenatal screening tests suggestive of a birth defect
● Invasive tests suggestive of birth defects
● Family history of a genetic trait or disorder
● Previous child with a birth or genetic condition
● Maternal age over 35 years.

14. Allele
An allele is the variant form of a gene as detected by various phenotypes say a color variation of white and
purple petals as demonstrated by Gregor Mendel.
Apart from some notable exceptions, diploid organisms express both alleles at a given locus in the normal
state. However, a monoallelic expression is much more widespread thus need to study it to describe various
disease processes.

15. Monolithic Expression
Monoallelic gene expression is the type of gene expression in which one copy of the gene is active, and
the other copy is silent. Once it is initiated early in the development of an organism, the monoallelic
expression is stably maintained after that. The more prevalent form of gene expression is a biallelic
expression. It is the transcription of both alleles of a gene.
Each allele is not expressed equally. An allelic imbalance is exhibited in 5 – 20% of the autosomal genes.
Balanced expression
The monoallelic expression can occur in a number of ways:AND ALL ALLELES ARE EXPRESSED EQUAL.
● Genomic imprinting
● Random choice of one allele
● X-inactivation

16. Genomic Imprinting
● Genomic imprinting is a type of monoallelic expression that is determined by these epigenetic marks;
thus, the copies of imprinted genes of the fertilized egg that came from the paternal and maternal
contributions have different marks.
● Human organisms are diploid in nature and all somatic cells have two copies of a genome derived from
the mother and another from the father. In genomic imprinting, however, it is only from the paternal
allele that some imprinted genes are expressed, while others are expressed only from the maternal
allele
● Same active allele is present in all cells in which a given gene is imprinted. This active allele is
determined by the parent of origin of the allele. Genomic imprinting is also known as parent of origin
imprinting.
● All imprinted genes encode a protein. Different proteins have different and a wide variety of functions
within the cells.
● Same active allele is present in all cells in which a given gene is imprinted. This active allele is
determined by the parent of origin of the allele. Genomic imprinting is also known as parent of origin
imprinting.

17. Somatic rearrangement: in this type, there is a change in DNA organization to produce functional gene at
one allele, but not at the other. Genes affected by this type of random monoallelic expression are:
● Pheromone receptor genes
● Interleukin genes
● Genes encoding receptors on natural killer cells
Allelic silencing: in this process, only one allele of a gene is expressed, while the other allele is
silenced.Somatic rearrangement: in this type, there is a change in DNA organization to produce functional
gene at one allele, but not at the other. Genes affected by this type of random monoallelic expression are:
● T-cell receptor genes
● Immunoglobulin genes

18. Barr body: a heterochromatic mass seen during interphase is known as a Barr body.
Dosage compensation:Dosage compensation is a term that describes the processes by which organisms
equalize the expression of genes between members of different biological sexes. It results in random
epigenetic silencing of one X chromosome.
Often, changes in the level of gene expression go unnoticed; however, sometimes even a small change can
have severe clinical consequences.

19. Goldilocks Principle
Goldilocks principle states that something must fall within certain margins, as opposed to reaching extremes.
It is derived from an initial analogy of a child named Goldilocks who chose a bowl of porridge that was neither
too hot nor too cold as the preferred choice. This principle of just the right amount is applied in genetics
indicate that something must be just right, neither too much, nor too less. Many genetic principles involve
changes in the amount of gene product. When the amount of gene product changes, it no longer follows the
‘just right’ principle of Goldilocks.

20. Restriction Fragment Length Polymorphism (RFLP)
One of the most common DNA fingerprinting technique is the restriction fragment length polymorphism
(RFLP). This technique uses special enzymes to cut segments of a sample where DNA can be extracted. It
involves looking for repetitive DNA base sequences in individual DNA using specific restriction
endonucleases. It specifically looks for differences in the homologous DNA sequences.
RFLP markers are highly locus-specific, which is why they can be used to detect genetic diseases. An
RFLP probe is a labeled DNA sequence that can hybridize with 1 or more fragments of the DNA sample.
When they are separated using electrophoresis technique, different viewing techniques may be used,
including UV light or autoradiography, in the case of use of radioactive markers. When a mutation occurs,
there are changes in the profile of the normal and mutated DNA fragments obtained after electrophoresis.

21. Short Tandem Repeats Polymorphisms (STR)
Another technique used in DNA fingerprinting is a short tandem repeat (STR) polymorphisms. STR are
short DNA sequences that are repeated a dozen or more times in a head-to tail-manner. This technique does
not involve using restriction enzymes like the ones used in RFLPs. It uses probes that attach to a specific
region in the DNA. The polymerase chain reaction is then done to determine the length of the short
tandem repeats.
STR regions are variable or polymorphic, which is why they can be used to discriminate 1 DNA profile from
another; 1 individual can have 5 repeats of a specific sequence while another may have 7. The number of
repeats can be used to profile individuals.

22. Prenatal Screening and Diagnosis
Tests available for prenatal diagnosis include:
● Ultrasonography: evaluating nuchal translucency
● Amniocentesis
● Chorionic villus sampling
● Fetal blood cells in maternal blood
● Maternal serum alpha-fetoprotein
● Maternal serum beta-HCG
● Maternal serum estriol

23. Sanger Sequencing

24. Human Genome Project

27. Genome as String ,Reads as substring
DNA polymerase is an enzyme that synthesizes DNA molecules from
nucleoside triphosphates, the molecular precursors of DNA. These
enzymes are essential for DNA replication and usually work in groups
to create two identical DNA duplexes from a single original DNA
duplex

28. Terminator DNA bases

29. Sequencing errors and base qualities

30. Second-generation Sequencing

31. Fastq format

32. Boyer Moore Basics

33. K-mer index

34. pigeonhole principle

40. Prune belly Syndrome

41. Anorexia nervosa

42. Kaggle for the practice
https://www.kaggle.com/crawford/gene-expression (sometimes we get unexpected json input)

43. For the software part we will jump on to the
notebooks
Before that I love to give a brief intro on the hardware that might be required I too
don't know much so please do bear with me.

44. Custom Hardware
● ASIC’s
● FPGA
● GPU/GPGPU
● TPU
● PSOCS
● SOC
● Configurable Arrays
● PCIE ports
● And duniya barki cheese.

45. But can never replace your
● Brain
● Heart
● Kidney
● Liver
● etc etc etc.

46. This is what the world is moving towards.
Human like computing modules.

47. Now lets just not waste time join the community for
the more information
Google Crowdsource RNSIT Computer Architecture Club