Showing posts with label Genetics. Show all posts
Showing posts with label Genetics. Show all posts

Saturday, May 29, 2021

The Happy face

 Hi everyone!

Lets talk about a 2 year old girl with a h/o seizure disorder who presents to your clinic for the first time for routine care. Past medical records shows that the patient is on anti-seizure medication since the last year. There is no family history of seizures. Parents report poor feeding and sleep disturbances. The girl appears to be very happy, laughing all the time for no reason. On examination, her head circumference is in the 10th percentile and is noted to have hand flapping behavior. She has not met the expected milestones for her age. What is the diagnosis?



Fun fact: Angelman Syndrome was previously known as "Happy Puppet Syndrome"😄

- Padma Sri Katikaneni

Sunday, May 23, 2021

Ehler-Danlos Syndrome (EDS) - High yield only

Hi! So let's learn EDS together. I've tabled a list of high-yield points of all the types of EDS. It requires little bit of revision but once you get a pictorial familiarity you should be able to recall them all. 

Have fun!

So, how to remember?

Step 1. Divide the table into 2 halves. Sl no. 1,2,3 have in common a lot of features:
  • They are all Autosomal Dominant. 
  • They have common Clinical features - skin HYPERelasticity, joint HYPERmobility and HYPER (easy) bruising. 
  • Go serially, Classical has the first 2, Type I and II and HYPERmobile is III and lastly Vascular is type I
  • Vascular type has additionally - arterial & uterine rupture.
Step 2. Now the second section Sl no. 4,5,6
  • EDS types with enzyme defects are Autosomal Recessive. So, 4 and 6 are AR. 
  • Kyphoscoliotic EDS is Type VI (K rearranged is a V and I)
  • For the last 2, mnemonic is ABCD😛 Arthrochalasia VII a, b and VII c is Dermatosparaxis.
  • KyphoSCOLIOTIC EDS - defective lysyl hydroxylase (=> abnormal cross linking of collagen or KOLLAGEN => think of bones ðŸĶī => congenital SCOLIOSIS)
  • ARTHROchalasia is COL IA (1st letter is A) and hence presents with severe JOINT hyper mobility.
  • DERMATospARaxis is AR and a defective Procollagen-N-peptidase and presents with CUTIS laxa. (Cuties are Pros ;)

Step 2. For the Gene types, come down in descending order: 5 4 3 2 1

Step 3. Remember Type V - DOEST NOT EXIST. 

Step 4. Revise again 😉

That's it! Stay safe ðŸŒļ
- Anagha :)

Wednesday, May 12, 2021

Kartagener syndrome mnemonic


Kartagener syndrome (primary ciliary dysfunction, aka immotile cilia syndrome) mnemonic :-

Monday, April 26, 2021

Menkes disease and Wilson's disease - DDx


Okay so maybe they are the two of the options for a patient's clinical scenario question and you have a blurred memory for which is which in context to copper metabolism?

Let's clear the basic facts here...

Thursday, March 11, 2021

Genomic imprinting and Trinucleotide repeat -EXTRA EDGE

Hello Awesomites! 

1.Genomic imprinting IOC = methylation specific MLPA 

2.Trinucleotide repeat disorder = IOC is Trinucleotide primed PCR 

3.Fragile X Syndrome is XLR (mendelian inheritance) but once inherited during gametogenesis what happens is non - mendelian inheritance.

Confusing but thats the beauty. 

Can you tell me about Huntington disease what does mendelian and non mendelian inheritance mean? 

4.Angelman  that undergo whatever you learn (like maternal deletion and unipaternal disomy) involve chromosome 15 but gene is UBE3 ubiquitin protein. 

And praderwilli whatever you learn happens at chromosome 15 but gene is Sn RPN (small nuclear ribonucleoprotein polypeptide N)

 Hope it broadens your horizon.

-Dr.Upasana Y. 

Saturday, April 25, 2020

COVID-19: Whose Virus Is It Anyway? Possible origins of SARS-CoV-2

It's only reasonable you may want to know about the origins of the COVID-19 pandemic. After all, our lives have been affected, one way or the other. But was it the bat? Was it the pangolin? Or was it a lab experiment gone wrong? Let's look at the two most definitive evidence we have at hand: virus genomics and structure.

Evidence #1

The receptor binding domain (RBD) in the spike protein is the most variable part of the coronavirus family genome. SARS-CoV-2 seems to have an RBD that binds with high affinity to ACE2 from humans, and other species with high receptor homology. This RBD has six key amino acid residues.

Evidence #2

The second notable feature of SARS-CoV-2 is a polybasic cleavage site at the junction of S1 and S2, the two subunits of the spike. This allows effective cleavage by furin and other proteases and has a role in determining viral infectivity and host range. Insertion of proline to this site and subsequent addition of O-linked glycans are unique to SARS-CoV-2.

Keeping these in mind, we have:

Theory #1
Natural selection in animal before zoonotic transfer

As many early cases of COVID-19 were linked to the Huanan market in Wuhan, it is possible that an animal source was present at this location.

Given the similarity of SARS-CoV-2 to bat SARS-CoV-like coronaviruses, it is likely that bats serve as reservoir hosts for its progenitor. This "bat virus" or more formally, RaTG13 is nearly 96% identical to SARS-CoV-2. Its spike diverges in the RBD, which suggests that it may not bind efficiently to human ACE2. 

Malayan pangolins illegally imported into Guangdong province contain coronaviruses similar to SARS-CoV-2. Some "pangolin coronavirus" exhibit strong similarity to SARS-CoV-2 in the RBD, including all six key RBD residues. This clearly shows that the SARS-CoV-2 spike protein optimised for binding to human-like ACE2 is the result of natural selection.

Neither the bat nor the pangolin coronavirus, however, has polybasic cleavage sites. This means, no animal coronavirus has been identified that is sufficiently similar to be the direct progenitor of SARS-CoV-2. That said, the diversity of coronaviruses in bats and other species is massively undersampled. Mutations, insertions and deletions can occur near the S1–S2 junction of coronaviruses, which shows that the polybasic cleavage site can arise by a natural evolutionary process. This perfectly sets us up for our next theory.

Theory #2
Natural selection in human after zoonotic transfer

It is possible that a progenitor of SARS-CoV-2 jumped into humans to acquire the genomic features described above through adaptation, during undetected human-to-human transmission. Once acquired, these adaptations would enable the pandemic to take off.

All SARS-CoV-2 genomes sequenced so far have the genomic features described above and are thus derived from a common ancestor that had them too. The "pangolin coronavirus" has an RBD very similar to that of SARS-CoV-2, by the process of natural selection. From this, we can infer the same happened with the virus that jumped to humans. So we can say, with some degree of confidence, the insertion of polybasic cleavage site occured during human-to-human transmission.

From what we know the first case of COVID-19 has been traced back to November 2019. This presumes a period of unrecognised human-to-human transmission, between the initial zoonotic event and the acquisition of the polybasic cleavage site.

Theory #3
Lab experiment gone wrong

Basic research involving passage of bat SARS-CoV-like coronaviruses in cell culture and animal models has been ongoing for many years in biosafety level 2 laboratories across the world, and there are documented instances of laboratory escapes of SARS-CoV. In theory, it is possible that SARS-CoV-2 acquired RBD mutations during adaptation to passage in cell culture.

Having said that, the "pangolin coronavirus" with nearly identical RBDs, provides a much stronger explanation of how SARS-CoV-2 acquired these via recombination or mutation. The high-affinity binding of the SARS-CoV-2 spike protein to human ACE2 is most likely the result of natural selection on a human or human-like ACE2.

The acquisition of both the polybasic cleavage site and predicted O-linked glycans also argues against culture-based scenarios. New polygenic cleavage sites have only been observed after prolonged in-vivo passage whereas generating O-linked glycans likely involves an immune system.

Furthermore, if genetic manipulation had been performed, one of the several reverse-genetic systems available for coronaviruses would probably have been used. However, the genetic data irrefutably show that SARS-CoV-2 is not derived from any previously used virus backbone.

These are strong arguments that SARS-CoV-2 is not the product of purposeful manipulation.

Theory #2 seems most likely, given the information currently available, but more scientific data could swing the balance of evidence to favour one hypothesis over another. What's important is to further study the possible origins, not just for understanding the current zoonotic pandemic but also to prevent the potential future ones.

1. 'The proximal origin of SARS-CoV-2' by Andersen et al:
2. 'A pneumonia outbreak associated with a new coronavirus of probable bat origin' by Zhou et al:
3. 'A new coronavirus associated with human respiratory disease in China' by Wu et al:

Ashish Singh

Monday, December 17, 2018

Chediak Higashi syndrome.

Hello! This is Ultra short post regarding Chediak higashi syndrome! Hope you like it.

In normal person, when bacteria is engulfed by WBCs, they are carried to lysosome enzyme by LYST protein.
LYST protein stand for Lysosomal transfer protein.

Defect in LYST protein causes Chediak Higashi syndrome. It is autosomal recessive disorder.
No LYST protein so no phagocytosis of macrophages. Hence recurrent infections.

Clinical features:

1) Recurrent infections.

2) Absence of Melanin - Albinism.
LYST also helps in transfer of melanin to superficial layer of skin

3) Decrease in Myelin formation - Delayed conduction.

4) Hemorrhage.
LYST helps in maturation of megakaryocytes to platelets.

Confirmation: Incomplete digestion of bacteria leads to formation of  "Giant granules inside cell"


C- CNS involvement
HE- Hemorrhage
DI- Decrease immunity

That's it!

-Demotional bloke.

Sunday, December 2, 2018

Obesity in Prader-Willi syndrome and WAGR syndrome

The delicate balance between food consumption and energy expenditure involves the modulation of orexigenic and anorexigenic signals at the hypothalamus.

OREXIGENIC PATHWAY- It involves peripheral mediators like ghrelin and neuropeptide-Y. 
They act on NPY-AgRP(neuropeptide-Y and agouti-related peptide) neurons which subsequently mediates orexigenic signals via second-order neurons that release peptides like orexin at the hypothalamus.

ANOREXIGENIC PATHWAY- It involves peripheral mediators like leptin, amylin, and PYY(Peptide YY).
They act on POMC/CART(Pro-opio melanocortin/Cocaine and amphetamine-regulated transcript) neurons.
These neurons release an alpha-melanocyte-stimulating hormone which in turn stimulates second-order neurons that release TRH, CRH and hence mediate catabolism.
They also simultaneously inhibit the anabolic pathway.

Now back to the pathogenesis of obesity in these syndromes.

In Prader-Willi syndrome levels of PYY are low due to loss of imprinted genes on chromosome 15q11-q13.
This results in reduced catabolism and enhanced uninhibited anabolism.
It is not uncommon for such patients to have BMI above 40.

In WAGR syndrome there is haploinsufficiency of BDNF(Brain-derived neurotrophic factor).
Alpha melanocyte-stimulating hormone in the catabolic pathway acts through melanocortin receptors(MC4R) on second-order neurons.
Downstream signaling pathways of MC4R involve BDNF hence explaining obesity in these patients.

In fact, efforts are already underway to reduce PPY levels and modulate BDNF to control obesity in these disorders.

Kirtan Patolia

Monday, September 10, 2018

Transcription : A mnemonic to remember the RNA Polymerases

Here's a short mnemonic post for you!

Transcription is the process by which the DNA is converted into an RNA transcript ( Literally - the DNA is transcribed or written out as an RNA sequence).

The key enzyme needed for this process is RNA Polymerase.

In Eukaryotes , there are 3 different RNA Polymerases subtypes depending on which RNA they help code for. 

We know that Ribo Nucleic Acids or RNA can be mRNA - Messenger RNA , tRNA or Transfer RNA , rRNA - Ribsomal RNA or one of the small nuclear RNAs - micro RNA - miRNA / siRNA.

Here's a mnemonic to memorize which RNA Polymerase codes for which of these -

Mnemonic - R MIS T5 (Read as R Mistify)

RNA Polymerase I = rRNA
RNA Polymerase II = mRNA, miRNAs , siRNAs
RNA Polymerase III = tRNA , 5S rRNA

This form of RNA specificity is not found on the Prokaryotes - and they have just one RNA Polymerase that bears it all , for all types of RNA !

This has been a quick summary of transcription and a helpful mnemonic for you!

Hope was helpful.
Stay awesome !
Happy Studying!

~ A.P.Burkholderia

Thursday, January 25, 2018

Lymphoma and Leukemia Translocations Mnemonic

Hello everyone!

Here's an intuitive way to remember the chromosomal translocations involved in various lymphomas and leukemias.

Hope this helps. Happy studying!

-- Ashish Singh

Thursday, October 12, 2017

BRCA1 vs BRCA2 gene mutations and associated chromosomes (mnemonic)

BRCA1 gene mutation is located on choromosome 17 while BRCA2 gene mutation is located on chromosome 13, how to remember that?

- 1 and 3 in number 13 if joined together, they look like a breast 1+3 =>13
- this reminds me of its association with breast cancer.

BRCA1 is really famous:
-Another Famous mutation is P53 gene mutation which causes LI Fraumeni syndrome.
-Flip IL in LI Fraumeni and you get the number 17.
-Asssociate LI Fraumeni (p53) and  BRCA1 together since both are very famous => both are due to chromosome 17 mutations.

and that's it :)


Monday, October 2, 2017

Corpus Callosum - Let's connect

Hey Awesomites
Jas here
I am back :)

Let's talk about the largest connective pathway in the brain, the Corpus Callosum that is made up of more than 200 million nerve fibres, connecting our left brain to the right.

Saturday, September 23, 2017

Chromosomes affected in syndromes that sound similar, a mnemonic

Hello everyone!

Wilson's disease, Williams syndrome and Wilm's tumor are confusing since they all start with "Wil". This is how I remember them and differentiate which chromosome number is affected in which disease. 

Wilson's disease: (for Dr. House fans)
Remember Dr. House, Wilson and Thirteen?

So that's how I remember that in Wilson's disease chromosome 13 is affected. 

William syndrome:
If you read the 2nd part of the word William, it is: I AM. When you re-arrange it: I AM WILL. 

Remember Will Smith and his famous movie - Seven Pounds? 

William syndrome => chromosome 7 affected. 

Wilm's tumor:
Just write the I and L as 11 so it is W11m's => Chromosome 11 is affected.


Friday, September 22, 2017

Trinucleotide repeats mnemonics

In Friedreich Ataxia, patients have problems in their gait => GAAAAAAAAAAAit :D
so the trinucleotide repeat is: GAA

In Fragile X syndrome, patients have problems in their testicles (large testes among other things) so they  "Can't Get it Going" :P  => the trinucleotide repeat is: CGG


Tuesday, July 25, 2017

Genetics in Alzheimer's disease mnemonic

__________ gene is associated with early onset Alzheimer's disease (AD).

__________ gene is associated with late onset Alzheimer's disease.

Early onset - APP gene
Late onset - Apo E4 gene

Awesomite: I need a mnemonic for this.

apO E4 in Old Elderly
aPP in Pediatric Patients


Sunday, July 16, 2017

Favorites of brain cells: The game of genetics

Hey Awesomites

Many cells in the brain express two copies of a gene - maternal and paternal. But some express only one. If the single copy that is expressed carries a genetic mutation, it may result in cellular dysfunction and thus there are consequences.

Research on newborn mouse suggests that in about 85 percent of genes in the dorsal raphe nucleus, known for secreting serotonin, differentially activate their maternal and paternal gene copies. Ten days later in the juvenile brain, both copies are activated equally for all but 10 percent of genes.

The disparity also occurs in humans and in other systems like liver and muscles.

Like for example, in humans, a gene called DEAF1 that is implicated in autism and intellectual disability, shows a preferential expression of one copy of genes in multiple areas of brain. This is true for genes in other mental and neurologic disorders like Huntington's disease, schizophrenia, ADHD, and bipolar disorder.
Source )

Thats all
- Jaskunwar Singh

Fact of the day: Liquid biopsy for cancer detection

Hey Awesomites

We have known since long that surgical biopsies done routinely in cancer patients to diagnose and detect progression of the disease may increase the risk of carcinogenic changes in the cells in future, due to the changes that had prompted the biopsies.

A non - invasive and painless diagnostic tool that replaces the cutting is "liquid biopsy" that finds the hidden cancer cells anywhere in the body. The liquid biopsy is taken from a simple blood test to look for microscopic pieces of DNA circulating in the blood that contains genetic mutations causing tumors to spread, among billions of other DNA that were in the blood.
A year ago, a circulating tumor DNA test was approved by FDA that spots these mutations.

Thats all
- Jaskunwar Singh

Saturday, May 27, 2017

Syndromes associated with Ventricular Septal Defect : Mnemonic

Here's a short post.
So a fair bit of genetic mutations are associated with VSD's.

Remember :
(As in You ACED your exam ! )

A- Apert Syndrome
Features are mainly Cranio-digital. Causes Craniosynostosis, Syndactyly and mandibulo-facial deformities.

C- Cri du chat Syndrome
Notorious for the kitten like cry.
Other features are hyperagrresivenes, skin tags in front of eyes , microcephaly and wide eyes.

E - Edwards Syndrome
Trisomy 18. Other features - Omphalocele , esophageal atresia, low set ears, Microcephaly, Ptosis and Rocker bottom feet , Hypertelorism. Also associated with ASDs.

D - DiGeorge Syndrome
A - Abnormal facies
T - thymic aplasia
C - Cleft palate
H - Hypocalcemia
22 - Chr 22 abnormality.

D - Down Syndrome
(You all know about that one !)

That's all!
Hope this helped.
Happy Studying and like always , Stay awesome !

~ A.P.Burkholderia

Saturday, May 13, 2017

Research update : Genetic locus of Anorexia nervosa revealed

Hey Awesomites

A Research landmark study led by UN school of medicine has found the first genetic locus for the perplexing illness, anorexia nervosa. Previously it was known that this eating disorder runs in families with genetic and environmental factors both playing their role and there is ten - fold risk in first -degree relatives, but no particular association with a genetic locus was provided.

Thought to be associated with psychiatric disorders like neuroticism and schizophrenia, it has also been positively correlated with underlying metabolic abnormalities including body - mass index (BMI) and insulin - glucose metabolism. Genome - wide association studies ( GWAS ) have revealed a significant locus for anorexia nervosa on chromosome 12, in a region previously shown to be associated with type -1 diabetes mellitus and autoimmune disorders. This means that this eating disorder shares common roots with metabolic and psychiatric traits !!

These results may help in reconceptualizing the underlying aetiology and pathogenesis of such a lethal disorder and also coming up with new treatment interventions to cure the disease.

Thats all
- Jaskunwar Singh

Friday, May 12, 2017

X-Linked Dominant Disorders.

Hello everybody!

Let's learn a quick way to remember a few important X-linked Dominant Disorders.

The mnemonic goes like:

All Hypo Pigmented Rats Have Resistant Rickets.

All - Alport Syndrome.
Hypo - Familial Hypophosphatemia.
Pigmented - Incontinentia Pigmenti.
Rats - Rett Syndrome.
Resistant​ Rickets - Vit.D Resistant Rickets.

X linked dominant disorders are rare pattern of inheritance.

All affected males will transmit it to all their daughters and all affected females will transmit the disease to 50% of her sons/daughters.

If you have another mnemonic on the same do share.

Let's learn Together!