Heidelberg university, Public university in Heidelberg, Germany

A rare genetic defect that affects the so-called ALG2 gene can cause serious metabolic diseases in humans, said experts, adding that it does so through the defective formation of proteins and sugar molecules. Till now, its rareness and complexity made it difficult to study this congenital glycosylation disorder.A research team led by Prof. Dr Joachim Wittbrodt and Dr Thomas Thumberger from the Centre for Organismal Studies (COS) of Heidelberg University finally succeeded in introducing the underlying mutation in the ALG2 gene in a fish model, thus allowing the causes of these complex diseases to be studied at the molecular level. The study was published in the journal Development.Human cells are kept alive by the activity of millions of proteins. As they mature, these proteins must be modified in a myriad of ways, such as through the addition of sugar molecules - a crucial change for proper function. Defects in this sugar-adding process, also known as sugar decoration, are often lethal at the very early stages of development.As Prof. Wittbrodt explains, in rare cases a genetic defect causes sugar-addition deficiencies, which then manifest as congenital disorders of glycosylation. "Correct protein glycosylation requires a number of enzymes functioning together like clockwork," stated the researcher.The ALG2 gene has an especially important task in this process. It codes an enzyme needed for the correct branching of the sugar chain. If this process is disturbed, patients appear unaffected at birth but develop problems in different organs, such as the eyes, brain, and muscles, during early childhood.The team led by Prof. Wittbrodt and Dr Thumberger used the CRISPR/Cas9 gene-editing scissors to introduce an ALG2 mutation in a fish model, the Japanese rice fish or medaka. "Fish are particularly good models for these disorders because they develop outside the mother, making them very suitable for studying early embryonic defects," explained Dr Thumberger.In addition, the genome of the Japanese rice fish can be edited efficiently and precisely. "Our fish are genetic twins, so to speak, so the effect of individual changes can be directly identified as compared to non-genetically altered fish."Although the evolutionary distance between humans and fish is vast, the researchers report many of the same symptoms in the fish model that appear in ALG2 patients, including specific neuronal defects. They were surprised by the results yielded by the analysis of the total medaka organism, which took into account the full spectrum of different cell types."Although all cells of the fish showed the same reduced ALG2 activity, some cell types were more affected than others," said Prof. Wittbrodt. In the retina of the fisheye, cone cells needed for color-sensing were unaffected, but there was a progressive loss of rod cells needed for vision in low light, thus rendering the fish night-blind. Now the researchers hope to identify the proteins that cause the rod cells to die off because of diminished sugar-binding.Building on this research, the Heidelberg research team plans to study the molecular mechanisms and causes for the development of such complex metabolic diseases in humans.( With inputs from ANI )Disclaimer: This post has been auto-published from an agency feed without any modifications to the text and has not been reviewed by an editor

Heidelberg UniversityFOLLOW

Heidelberg university, Latest News

Luka Doncic produced an incredible triple-double performance to lead Slovenia to the Olympics for the very first time as they defeated Lithuania 96-85 on Sunday here at Kaunas in FIBA Olympic Qualifying Tournament finals. ...

Berlin, July 2 The Delta variant is expected to become the dominant Covid-19 strain in Germany with its ... ...

On the occasion of the first anniversary of Hong Kong's national security law, members of the European Parliament wrote a joint letter to top EU leaders, demanding action against the Chinese authorities for the imposition of a legislation law that "d ...

Germany has recently withdrawn the last contingent of its troops from Afghanistan after nearly 20 years of mission in the country. A contingent of around 570 soldiers was called back from Afghanistan on Tuesday (local time) as the security situation ...

Berlin, June 30 Germany's manager Joachim Loew's 15-year spell ended on a sour note with the former world ... ...

Germany midfielder Toni Kroos admitted his side "lacked effectiveness" as they were eliminated in the round of 16 after England struck two second-half goals in the ongoing Euro 2020 at Wembley Stadium. ...

London, June 29 Fourth seed Alexander Zverev of Germany began his quest for a maiden Grand Slam title ... ...

A rare genetic defect that affects the so-called ALG2 gene can cause serious metabolic diseases in humans, said experts, adding that it does so through the defective formation of proteins and sugar molecules. Till now, its rareness and complexity mad ...