Menu

Close

Human Handedness: Genetics, Microtubules, Neuropsychiatric Diseases and Brain Language Areas

Akira Wiberg, Gwenaelle Douaud, Michael Ng, Yasser Al Omran, Fidel Alfaro-Almagro, Jonathan Marchini, David L Bennett, Stephen Smith, Dominic Furniss

Preprint posted on October 26, 2018 https://www.biorxiv.org/content/10.1101/454660v1

Have you ever thought about the factors that make you a right- or a left- hander? This preprint looks into the genetics of human handedness, the first genome-wide study of its kind

Selected by Jose Guerrero

Categories: genetics

Left or right? The secret (genetic) code of handedness

Lateralization and predilection for one hand may be one of the most intriguing traits of humankind. Today, only about 10% of the population is left-handed. This proportion used to be even greater a century ago when sociocultural attitudes towards lefties were quite common in western countries.

Research studies on handedness, which have included monozygotic and dizygotic twins and their siblings, have estimated a 25% heritability of this trait. In the current GWAS and big data era, we have the preprint of the first genome-wide study of handedness using more than 350,000 right-handers and 35,000 left-handers.

The most significant genetic associations with handedness are found proximal or within genes coding cytoskeletal proteins such as b-tubulin –encoded by TUBB– and microtubule-associated proteins such as Map2 and Tau –encoded by MAP2and MAPT, respectively-.  The association with MAPTis part of a large haplotype block whose lead variant lies within an intron of WNT3. This gene codes a member of the Wnt signaling pathway, highly relevant in patterning during embryogenesis and axis formation in vertebrates. In fact, these biological processes do not seem to be so far from lateralization and handedness. In line with previous GWAS, the majority of associations are found in intergenic regions and gene introns suggesting a potential role as regulatorsof gene expression. These variants could modulate the DNA’s 3D structure and affect chromatin state and interactions between distant loci and their promoters1. Indeed, the authors reference that two of the variants found are also eQTL’s of MAPTand another gene, MICB, located ~0.8 Mb downstream of TUBB, respectively.  These are exciting associations that require follow-up biological studies.However, as opposed to other GWAS where model systems are generated to explore molecular mechanisms driven by genetic variants, can biological systems be developed to address handedness?

Interestingly, this study also associates handedness with different morphological features of some areas of the brain, e.g. higher connectivity between left and right brain hemispheres in left-handers. However, is this cause or consequence of left-handers living and having been adapted to a right-handers world? Does this associate with a greater ability of left-handers to use their right hand rather than a right-hander using their left hand? Since some of the interconnected areas are related with language networks, is a correlation between handedness and language skills plausible?

Last but not least, there is also a correlation with neurological pathologies. This may not be so surprising after the association of handedness with MAPT, a locuspreviously associated with neurodegenerative disorders such as Alzheimer’s disease. MAPTencodes Tau, a protein that provides stability to axonal microtubules in neurones. Dysfunctional Tau gives rise to the so-called Tau tangles (or aggregates), which are a hallmark of Alzheimer’s disease and other neurodegenerative disorders.

As most good scientific studies, this one provides answers but also generates lots of new questions for a topic, which will continue to puzzle both the scientific and the lay world.

Further questions

Is there a specific expression pattern of the 4 selected genes in a particular brain hemisphere of left- and right- handers?

What is the prevalence of those variants through evolution and across species? Primates can also show handedness but what about quadrupeds and other vertebrates? Are the identified variants more prevalent in species that show handedness?

What about polygenic risk score for handedness? We can assume that this trait is far too complex to be genetically regulated by a limited number of variants or loci. Instead, developing a model of polygenic risk score as it has been reported for diseases such as cardiovascular disease and cancer2may be more realistic for scoring handedness.

References

1- Amartya Sanyal, Bryan R. Lajoie, Gaurav Jain, Job Dekker. The long-range interaction landscape of gene promoters. Nature  489: 109–113. 2012.

2- Khera AV, Chaffin M, Aragam KG, Haas ME, Roselli C, Choi SH, Natarajan P, Lander ES, Lubitz SA, Ellinor PT, Kathiresan S. Genome wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genetics 50:1219-1224. 2018.

 

Posted on: 25th February 2019 , updated on: 28th February 2019

Read preprint (No Ratings Yet)




  • Have your say

    Your email address will not be published. Required fields are marked *

    This site uses Akismet to reduce spam. Learn how your comment data is processed.

    Sign up to customise the site to your preferences and to receive alerts

    Register here

    Also in the genetics category:

    The Hunchback temporal transcription factor determines motor neuron axon and dendrite targeting in Drosophila

    Austin Q Seroka, Chris Q Doe



    Selected by Abagael Lasseigne

    1

    Preformed Chromatin Topology Assists Transcriptional Robustness of Shh during Limb Development

    Christina Paliou, Philine Guckelberger, Robert Schöpflin, et al.



    Selected by Rafael Galupa

    1

    Molecular Logic of Spinocerebellar Tract Neuron Diversity and Connectivity

    Myungin Baek, Vilas Menon, Thomas Jessell, et al.



    Selected by Yen-Chung Chen

    Over-activation of BMP signaling in neural crest cells precipitates heart outflow tract septation

    Jean Francois Darrigrand, Mariana Valente, Pauline Martinez, et al.



    Selected by Giulia Boezio

    Functional dissection of TADs reveals non-essential and instructive roles in regulating gene expression

    Alexandra Despang, Robert Schöpflin, Martin Franke, et al.



    Selected by Clarice Hong

    Crowdfunded whole-genome sequencing of the celebrity cat Lil BUB identifies causal mutations for her osteopetrosis and polydactyly

    Mike Bridavsky, Heiner Kuhl, Arthur Woodruf, et al.



    Selected by Jesus Victorino, Gabriel Aughey

    1

    Dynamic Erasure of Random X-Chromosome Inactivation during iPSC Reprogramming

    Adrian Janiszewski, Irene Talon, Juan Song, et al.



    Selected by Sergio Menchero

    Kinesin-6 Klp9 plays motor-dependent and -independent roles in collaboration with Kinesin-5 Cut7 and the microtubule crosslinker Ase1 in fission yeast

    Masashi Yukawa, Masaki Okazaki, Yasuhiro Teratani, et al.



    Selected by I. Bouhlel

    The Spatio-Temporal Control of Zygotic Genome Activation

    George Gentsch, Nick D. L. Owens, James C. Smith



    Selected by Meng Zhu

    Multilevel regulation of the glass locus during Drosophila eye development

    Cornelia Fritsch, F. Javier Bernardo-Garcia, Tim Humberg, et al.



    Selected by Gabriel Aughey

    1

    Distinct ROPGEFs successively drive polarization and outgrowth of root hairs

    Philipp Denninger, Anna Reichelt, Vanessa Aphaia Fiona Schmidt, et al.



    Selected by Marc Somssich

    A direct and widespread role for the nuclear receptor EcR in mediating the response to ecdysone in Drosophila

    Christopher M Uyehara, Daniel J McKay



    Selected by Natalie Dye

    MRE11-RAD50-NBS1 activates Fanconi Anemia R-loop suppression at transcription-replication conflicts

    Emily Yun-Chia Chang, James P Wells, Shu-Huei Tsai, et al.



    Selected by Katie Weiner

    1

    Super-resolution Molecular Map of Basal Foot Reveals Novel Cilium in Airway Multiciliated Cells

    Quynh Nguyen, Zhen Liu, Rashmi Nanjundappa, et al.



    Selected by Robert Mahen

    Single cell RNA-Seq reveals distinct stem cell populations that drive sensory hair cell regeneration in response to loss of Fgf and Notch signaling

    Mark E. Lush, Daniel C. Diaz, Nina Koenecke, et al.

    AND

    Distinct progenitor populations mediate regeneration in the zebrafish lateral line.

    Eric D Thomas, David Raible



    Selected by Rudra Nayan Das

    2

    The coordination of terminal differentiation and cell cycle exit is mediated through the regulation of chromatin accessibility

    Yiqin Ma, Daniel J McKay, Laura Buttitta



    Selected by Gabriel Aughey

    1

    Close