Fast & Furious Discovery

Fast and furious Mendelian gene discovery with no end in sight? That’s a title that gets us excited. Let’s start with the facts, by 2018, CMGs (Centers for Mendelian Genomics) had made 1937 novel gene discoveries, but reported only 287 of them. So the current pace may be faster than we think. But finding the next few thousand Mendelian conditions will rely on better data sharing worldwide.
AJHG

On a related note, researchers analyzed the Orphanet database to estimate the prevalence of rare diseases. Their conservative, evidence-based estimate for the population prevalence of rare diseases is 3.5–5.9%, which equates to 263–446 million persons affected globally at any point in time.
European Journal of Human Genetics

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The AI Corner

Pondering AI’s usefulness in the clinic?

Researchers develop a deep learning system for differential diagnosis of 26 skin diseases that result in 80% of patient visits to primary care facilities.
arxiv

Our own algorithm is also undergoing a study to determine its usefulness in clinical. Results will be a platform presention by Linyan Meng of Baylor Genetics at the coming ASHG:
‘Breaking the interpretation bottleneck: Examining the utility of an automated genomic interpretation algorithm in a clinical genetic lab‘
Saturday, October 18th, 11:00AM, Room 361D

We were also able to talk to Greenwood Genetic Center about how they were able to reduce time spent per case by 75% with our AI.

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Bridging the regulatory sequences gap

Researchers have been able to effectively capture long-range chromatin interactions and predict potential regulatory function for 27,325 noncoding sequence variants associated with 2,117 physiological traits & diseases.
Nature Genetics

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Break !

Pointy-haired Boss aside, that friend of yours who claims she doesn’t need to sleep – may be telling the truth!
Researchers discover a variant in ADRB1 that leads to natural short sleep trait in humans.
Neuron

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The value of sequencing infants with heart failure

Clinical utility of exome sequencing in infantile heart failure: genetic testing changed medical decision-making in 53% of all cases & 80% of positive cases.
Genetics in Medicine

Role of rare recurrent copy number variants in congenital heart defects: WES data from family trios identifies five novel CNV loci & provide insights on their impact on disease etiology.
Frontiers in Genetics

Genetic etiology of early infant deaths in a neonatal intensive care unit. Mutations in the genes associated with multiple congenital malformations can be the leading cause of death in NICUs. For newborns who died on the first day, the most common genetic cause of death was major heart defects.
BMJ

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Where do you store your fat?

A GWAS in UK Biobank cohort for predicted VAT mass suggests visceral adiposity is a potential independent risk factor for various cardiovascular & metabolic diseases and identifies 102 novel visceral adiposity loci.
Nature Medicine

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Male vs Female

Why do women have a greater risk of lupus & Sjögren’s? While men have a far greater risk of schizophrenia? The explanation may lie in C4 genes in the MHC locus, which lead to sex-specific vulnerability.
bioRxiv

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Aligning payers with patients

71% of payers in the US cover pediatric ES as they see merit in available interventions or in ending the diagnostic odyssey. However, skepticism still prevails when it comes to prenatal ES due to lack of in utero interventions.
Genetics in Medicine

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Significant Singles:

• SMPD4 and developmental disorder AJHG
• SPTAN1 and hereditary spastic paraplegia Journal of Human Genetics
• SOD2 and lethal neonatal dilated cardiomyopathy BMJ
• SIGMAR1 and distal hereditary motor neuronopathy of the Jerash type BMJ

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Ada Reports

(Ada is our AI engine, she likes to add an interesting new factoid she discovered in every issue)

Novel gene-disease connection reported: De novo missense variants in EIF2AK1 and EIF2AK2 are associated with wide array of phenotypes, including developmental delay, cognitive impairment, leukoencephalopathy & neurologic regression.
bioRxiv

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