Modern humans generate more brain neurons than Neanderthals due to a single amino acid change in the protein TKTL1

A single amino acid change in the transketolase-like 1 (TKTL1) protein may have given modern humans an advantage over more ancient contemporaries like Neanderthals by enabling increased neuron production. The researchers show that the modern human variant of the protein TKTL1, which differs by only a single amino acid from the Neanderthal variant, increases one type of brain progenitor cells, called basal radial glia, in the modern human brain. Read more about this study under Article 1.

Article 1: Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals

The increase in brain size and neuron production during brain development, are considered to be major factors for the increased cognitive abilities that occurred during human evolution. A single amino acid change in the transketolase-like 1 (TKTL1) protein may have given modern humans an advantage over more ancient contemporaries like Neanderthals by enabling increased neuron production. The researchers show that the modern human variant of the protein TKTL1, which differs by only a single amino acid from the Neanderthal variant, increases one type of brain progenitor cells, called basal radial glia, in the modern human brain. Basal radial glial cells generate the majority of the neurons in the developing neocortex, a part of the brain that is crucial for many cognitive abilities. As TKTL1 activity is particularly high in the frontal lobe of the fetal human brain, the researchers conclude that this single human-specific amino acid substitution in TKTL1 underlies a greater neuron production in the developing frontal lobe of the neocortex in modern humans than in Neanderthals. Read the full article here.

In summary: Modern humans generate more brain neurons than Neanderthals due to a single amino acid change in the protein TKTL1

Article 2: The impact of age on genetic testing decisions in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative syndrome. In up to 20% of cases, a family history is observed. Although Mendelian disease gene variants are found in apparently sporadic ALS, genetic testing is usually restricted to those with a family history or younger patients with sporadic disease. With the advent of therapies targeting genetic ALS, everyone treatable should be identified. Therefore, the researchers sought to determine the probability of a clinically actionable ALS genetic test result by age of onset. They found a significant probability of clinically actionable genetic test results in people with apparently sporadic ALS at all ages, with a significant proportion of patients over 40 years old. The results provide robust evidence to recommend that genetic testing in ALS should not be restricted by age of onset or family history. Read the full article here.

In summary: ALS genetic testing should not be restricted by age of onset or family history

Article 3: Identification of shared and differentiating genetic architecture for autism spectrum disorder, attention-deficit hyperactivity disorder and case subgroups

Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are highly heritable neurodevelopmental conditions affecting children and may last into adulthood. The researchers conducted a genome-wide association study of diagnosed ASD or ADHD and identified seven loci shared by disorders and five loci differentiating them. The shared genomic fraction contributing to both disorders was strongly correlated with other psychiatric phenotypes, whereas the differentiating portion was correlated most strongly with cognitive traits. Additional analyses revealed that individuals diagnosed with both ASD and ADHD were double-loaded with genetic predispositions for both disorders and showed distinctive patterns of genetic association with other traits compared with the ASD-only and ADHD-only subgroups. This provides support for the recent change in diagnostic guidelines allowing for the diagnosis of both ASD and ADHD in the same individual. Read the full article here.

In summary: Overlapping and distinct genetic contributions in autism and ADHD

Article 4: Measured blood pressure, genetically predicted blood pressure, and cardiovascular disease risk in the UK Biobank

Hypertension is a major cardiovascular disease risk factor, but variability in measured blood pressure is a key clinical challenge for optimal management. Genetic factors contributing to hypertension might help identify people at heightened risk for cardiovascular disease, even in those with normal blood pressure. To investigate whether the genetic factors that drive high blood pressure can help inform cardiovascular disease management, the researchers evaluated incident cardiovascular disease using a blood pressure polygenic risk score, independent of measured blood pressures and the use of antihypertensive medications. The results show that genetically predicted blood pressure risk was associated with cardiovascular risk, identifying 1 in 10 individuals with normal measured blood pressure who had comparable cardiovascular disease risk as those with untreated hypertension. This suggests that blood pressure polygenic risk scores may be used to complement measured blood pressure to achieve earlier and targeted cardiovascular disease prevention. Read the full article here.

In summary: Genetically predicted blood pressure risk score may help identify those at risk for cardiovascular disease

New in Genetics issue October 2022. Every month, Medicover Genetics curates the most important peer-reviewed scientific publications related to genetics.

References

[1] Pinson A et al. Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals. Science. 2022 Sep 9;377(6611):eabl6422. doi: 10.1126/science.abl6422. Epub 2022 Sep 9. PMID: 36074851. https://www.science.org/doi/10.1126/science.abl6422

[2] Mehta PR et al. The impact of age on genetic testing decisions in amyotrophic lateral sclerosis. Brain. 2022 Sep 27:awac279. doi: 10.1093/brain/awac279. Epub ahead of print. PMID: 36162820. https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awac279/6694277

[3] Mattheisen M et al. Identification of shared and differentiating genetic architecture for autism spectrum disorder, attention-deficit hyperactivity disorder and case subgroups. Nat Genet. 2022 Sep 26. doi: 10.1038/s41588-022-01171-3. Epub ahead of print. PMID: 36163277. https://www.nature.com/articles/s41588-022-01171-3

[4] Cho SMJ et al. Measured Blood Pressure, Genetically Predicted Blood Pressure, and Cardiovascular Disease Risk in the UK Biobank. JAMA Cardiol. 2022 Sep 28. doi: 10.1001/jamacardio.2022.3191. Epub ahead of print. PMID: 36169945. https://jamanetwork.com/journals/jamacardiology/article-abstract/2796903