̽��ֱ�� of Cambridge - chromosomes

One in 500 men carry extra sex chromosome, putting them at higher risk of several common diseases

cjb250 — Fri, 10 Jun 2022 07:56:38 +0000

In a study published in Genetics in Medicine, researchers analysed genetic data collected on over 200,000 UK men aged 40-70 from UK Biobank, a biomedical database and research resource containing anonymised genetic, lifestyle and health information from half a million UK participants. They found 356 men who carried either an extra X chromosome or an extra Y chromosome.

Sex chromosomes determine our biological sex. Men typically have one X and one Y chromosome, while women have two Xs. However, some men also have an extra X or Y chromosome – XXY or XYY.

Without a genetic test, it may not be immediately obvious. Men with extra X chromosomes are sometimes identified during investigations of delayed puberty and infertility; however, most are unaware that they have this condition. Men with an extra Y chromosome tend to be taller as boys and adults, but otherwise they have no distinctive physical features.

In today’s study, the researchers identified 213 men with an extra X chromosome and 143 men with an extra Y chromosome. As the participants in UK Biobank tend to be ‘healthier’ than the general population, this suggests that around one in 500 men may carry an extra X or Y chromosome.

Only a small minority of these men had a diagnosis of sex chromosome abnormality on their medical records or by self-report: fewer than one in four (23%) men with XXY and only one of the 143 XYY men (0.7%) had a known diagnosis.

By linking genetic data to routine health records, the team found that men with XXY have much higher chances of reproductive problems, including a three-fold higher risk of delayed puberty and a four-fold higher risk of being childless. These men also had significantly lower blood concentrations of testosterone, the natural male hormone. Men with XYY appeared to have a normal reproductive function.

Men with either XXY or XYY had higher risks of several other health conditions. They were three times more likely to have type 2 diabetes, six times more likely to develop venous thrombosis, three times as likely to experience pulmonary embolism, and four times more likely to suffer from chronic obstructive pulmonary disease (COPD).

̽��ֱ��researchers say that it isn’t clear why an extra chromosome should increase the risk or why the risks were so similar irrespective of which sex chromosome was duplicated.

Yajie Zhao, a PhD student at the Medical Research Council (MRC) Epidemiology Unit at the ̽��ֱ�� of Cambridge, the study’s first author, said: “Even though a significant number of men carry an extra sex chromosome, very few of them are likely to be aware of this. This extra chromosome means that they have substantially higher risks of a number of common metabolic, vascular, and respiratory diseases – diseases that may be preventable.”

Professor Ken Ong, also from the MRC Epidemiology Unit at Cambridge and joint senior author, added: “Genetic testing can detect chromosomal abnormalities fairly easily, so it might be helpful if XXY and XYY were more widely tested for in men who present to their doctor with a relevant health concern.

“We’d need more research to assess whether there is additional value in wider screening for unusual chromosomes in the general population, but this could potentially lead to early interventions to help them avoid the related diseases.”

Professor Anna Murray, at the ̽��ֱ�� of Exeter, said: “Our study is important because it starts from the genetics and tells us about the potential health impacts of having an extra sex chromosome in an older population, without being biased by only testing men with certain features as has often been done in the past.”

Previous studies have found that around one in 1,000 females have an additional X chromosome, which can result in delayed language development and accelerated growth until puberty, as well as lower IQ levels compared to their peers.

̽��ֱ��research was funded by the Medical Research Council.

Reference
Zhao, Y et al. Detection and characterisation of male sex chromosome abnormalities in the UK Biobank study. Genetics in Medicine; 9 Jun 2022; DOI: 10.1016/j.gim.2022.05.011

Around one in 500 men could be carrying an extra X or Y chromosome – most of them unaware – putting them at increased risk of diseases such as type 2 diabetes, atherosclerosis and thrombosis, say researchers at the universities of Cambridge and Exeter.

Even though a significant number of men carry an extra sex chromosome, very few of them are likely to be aware of this

Yajie Zhao

Rost-9D (Getty Images)

3D illustration XY-chromosomes

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Was the dawn of man among trees in the cradle of disease?

fpjl2 — Thu, 04 Jul 2013 08:22:23 +0000

When the family of Albert Perry - a recently deceased African-American man from South Carolina - sent a sample of his DNA to be tested by a genealogy website, they weren’t expecting to rewrite the history of mankind. They were probably just a bit curious.

But Perry’s DNA contained a Y chromosome not seen before, one which potentially reveals that the last common male ancestor in the paternal line of humanity is almost twice as old as previously thought – some 338,000 years, even though the oldest fossil of man is only 195,000 years old.

̽��ֱ��DNA was traced back to the Mbo ethnic group in central Africa, based primarily in South West Cameroon, suggesting that the dawn of modern man took place deep in the inhospitable forests of this region rather than the savannahs of East Africa, the area that conventional science has – until now – located as the site of the first homo sapiens.

This Friday, a student-run conference hosted by Cambridge’s Biological Anthropology Division will focus on this groundbreaking research, published earlier this year by a team from the ̽��ֱ�� of Arizona and UCL, to ask some of the major questions it raises: How might this change our understanding of human evolution? Does the forest still influence who we are today?

Relocating Origin will feature experts from Cambridge and elsewhere, including one of the UCL scientists who conducted the original research, Professor Mark Thomas, and will be available to watch through a live webcast.

“This is a hugely exciting time for human origin studies. If these early findings are proved correct, the current narratives of the beginning of our species have been predicated on a different location and a different time!” says Katie Fitzpatrick, a PhD candidate in the Department and one of the conference organisers.

“ ̽��ֱ��hot, humid forests work against fossil preservation as they just decay in such climates – unlike arid regions that have been the focus of early human research so far. However, the evidence may still be in the rainforests but we haven’t been looking”.

By asking ‘What if Adam lived in the forest?’ scientists will explore the implications not just for genetics but human culture, technology and society.

̽��ֱ��impact of a forest home on the social structure of the first homo sapiens will be examined by the Division’s Dr Peter Walsh, who researches social networks in primate ecology. A major theme of the conference will be what’s known as Behavioural Immune System hypothesis – the idea that social behaviour is an intrinsic part of the immune system, and infectious disease transmission can dictate social contact, especially in the heart of Africa.

“ ̽��ֱ��forest region of central Africa is the disease epicentre of the universe! HIV from chimps, bats carrying rabies, Ebola, SARS, insect vectors carrying malaria and parasitic diseases like river blindness and elephantitis, loads of fecal-oral diseases… It’s described as ‘pathogen rain’,” says Walsh.

“You live in a big group with lots of social interaction, and one of you gets Ebola – everybody dies. So it doesn’t make evolutionary sense in such places”.

Walsh suggests that the region’s ‘pathogen rain’ could have stunted early human development, as limited interactions due to fear of disease meant that ideas and innovations were unable to spread and build, leaving our first ancestors languishing in the forest for thousands of years.

“In disease hotbeds, people have much stronger group identification, which makes them much more hostile – part of the behavioural immune system. You see the same in gorillas.”

One possible theory Walsh will discuss is that, instead of a “key innovation” – such as walking upright or fire - triggering human development, just getting out of the disease-riddled forests could have allowed for much greater social interaction that sparked a “cascade of technological innovation”.

And it is a much more recent human innovation opening up these possibilities. We now live in the age of ‘big data’. ̽��ֱ��access to unprecedented reams of digital information is transforming almost every area of academic research in tandem with society in general: “This capacity to have genetic samples from vast numbers of people is giving us a whole new view of why we are the way we are, and this is only the start,” says Walsh.

While the evolutionary scientists stress that much more research needs to be done in the region, which presents all manner of challenges from unfavourable climates for fossilized evidence to political instability, the conference will be the first to look at the emergence of this brand new direction in the field, and how it can be taken “from speculation to science”.

“Certain methodologies need to be nailed down, which will take a few years, but this avenue of investigation could lead to the reassessment of a huge range of thinking around fire, meat-eating, bipedalism, locomotion – when and how these things happened are all potentially up for discussion,” adds Walsh.

“What we want to ask is how this might change things, to get people to start thinking about the possibility that the last fifty years of research has been mistaken in its assumptions about where we came from.”

For a full list of speakers and topics, and a link to the live webcast of the conference, go to http://relocatingorigin.soc.srcf.net/

Inset image: Dr Peter Walsh

A student-led conference to be webcast live will ask, in light of recent research, whether the story of human origin is radically different from established thinking, and what that might mean for everything from genetics to the birth of culture.

̽��ֱ��forest region of central Africa is the disease epicentre of the universe… It’s described as ‘pathogen rain’

Peter Walsh

Peter Walsh. Banner image credit Strollerdos

Forest region of South West Cameroon

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Scientists create mammalian cells with single chromosome set

gm349 — Tue, 13 Sep 2011 15:15:32 +0000

Cambridge researchers have created mammalian cells containing a single set of chromosomes for the first time in research funded by the Wellcome Trust and EMBO. ̽��ֱ��technique should allow scientists to better establish the relationships between genes and their function.

Mammal cells usually contain two sets of chromosomes – one set inherited from the mother, one from the father. ̽��ֱ��genetic information contained in these chromosome sets helps determine how our bodies develop. Changes in this genetic code can lead to or increase the risk of developing disease.

To understand how our genes function, scientists manipulate the genes in animal models – such as the fruit fly, zebrafish and mice – and observe the effects of these changes. However, as each cell contains two copies of each chromosome, determining the link between a genetic change and its physical effect – or ‘phenotype’ – is immensely complex.

Now, in research published last week in the journal Nature, Drs Anton Wutz and Martin Leeb from the Wellcome Trust Centre for Stem Cell Research at the ̽��ֱ�� of Cambridge report a technique which enables them to create stem cells containing just a single set of chromosomes from an unfertilised mouse egg cell. ̽��ֱ��stem cells can be used to identify mutations in genes that affect the cells' behaviour in culture. In an additional step, the cells can potentially be implanted into the mouse for studying the change in organs and tissues.

̽��ֱ��technique has previously been used in zebrafish, but this is the first time it has been successfully used to generate such mammalian stem cells.

Dr Wutz, a Wellcome Trust Senior Research Fellowship, explains: “These embryonic stem cells are much simpler than normal embryonic mammalian stem cells. Any genetic change we introduce to the single set of chromosomes will have an easy-to-determine effect. This will be useful for exploring in a systematic way the signalling mechanisms within cell and how networks of genes regulate development.”

̽��ֱ��researchers hope that this technique will help advance mammalian genetics and our understanding of the gene-function relationship in the same way that a similar technique has helped geneticists understand the simpler zebrafish animal model.

Understanding how our genetic make-up functions and how this knowledge can be applied to improve our health is one of the key strategic challenges set out by the Wellcome Trust. Commenting on this new study, Dr Michael Dunn, Head of Molecular and Physiological Sciences at the Wellcome Trust, says:

“This technique will help scientists overcome some of the significant barriers that have so far made studying the functions of genes so difficult. This is often the first step towards understanding why mutations lead to disease and, ultimately, to developing new drugs treatments.”

Researchers have created mammalian cells containing a single set of chromosomes instead of two.

These embryonic stem cells are much simpler than normal embryonic mammalian stem cells. Any genetic change we introduce to the single set of chromosomes will have an easy-to-determine effect. This will be useful for exploring in a systematic way the signalling mechanisms within cell and how networks of genes regulate development.

Dr Wutz, a Wellcome Trust Senior Research Fellowship, explains

Image Anton Wutz

Partial view of haploid chromosome set

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