The Sokko: exploring ethnic possibilities. Roots the Dutch version *** Op zoek naar Afrikaanse roots via DNA & genealogisch en historisch onderzoek.
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Feature Story: The Genome Ball
Forget Those X-Shaped Chromosomes
A Genome Looks Like This
Visitors to the Genome exhibition are frequently intrigued by the Genome Ball, a three-dimensional model of the human genome that represents a creative synthesis of scientific knowledge and technical innovation. For students and adults raised on clinically produced karyotypes – those artificially arranged pairs of X-shaped chromosomes photographed during cell division – the Genome Ball will challenge all their previous (mis)conceptions and show the human genome in a new light.
How did we first begin to grasp the structure of the nucleus? It all began in 1682 when Anton van Leeuwenhoek, a fabric merchant in the Dutch city of Delft, examined blood cells of fish. Leeuwenhoek used a microscope with lenses he’d ground himself, and reported his observations in a letter to the Royal Society:
I came to observe the blood of a cod and of a salmon, which I also found to consist of hardly anything but oval figures … it seemed to me that some of them enclosed in a small space a little round body or globule …
If you’ve looked at human blood under a microscope, that description may sound odd: Mature red blood cells (RBCs) don’t contain nuclei – do they? You’re right! However, the RBCs of fish (and amphibians and reptiles) do indeed have nuclei, and Leeuwenhoek was the first to describe them. Nevertheless, the Royal Society wasn’t blown away by his letter (after all, how much could a business man with “little fortune and no formal education” know about science?). The “little round body or globule” remained nameless for the next 150 years.
Then, in 1831, the Scottish botanist Robert Brown was studying plant fertilization when he noticed that pollen moved in and out of “ovals” in the plant cells. He called each oval a “nucleus,” a Latin word meaning “nut” or “kernel” – a bit like a black walnut surrounded by its thick green hull. Not only did Brown’s name stick, but his 1833 paper even suggested that the nucleus was probably involved in fertilization and the development of embryos.
The next step in our nuclear narrative was taken by Friedrich Miescher, a Swiss physician who extracted and isolated a previously unknown substance from pus-soaked bandages at the hospital where he worked. White blood cells, a major constituent of pus, have very large nuclei, and Miescher correctly concluded that the substance came from those nuclei. He called it “nuclein.” Today we call it DNA.
How many chromosomes in a human cell?
Although the fine points of cell division were still unexplained, scientists in the early 1900s were eager to learn the number of chromosomes in human cells. However, counting the number of human chromosomes during cell division turned out to be quite a challenge. Even when chromosomes were lined up on the “midline” of a cell, scientists’ counts ranged from 16 to 36.
Evidently, Hans von Winiwarter got tired of these wide-ranging approximations. Using the best microscopes available to him in 1912, he produced early karyotypes by capturing and fixing human cells at the moment of cell division. Despite his best efforts, Winiwarter’s counts ranged from 46 to 49; and while noting correctly that women have two X chromosomes, he mistakenly concluded that males had only one X and no Y. For the next 40+ years, students were generally taught that human cells contained 48 chromosomes.
Finally, in 1956, the correct value of “46” was confirmed – 22 pairs of autosomes and 1 pair of sex chromosomes in human cells other than eggs or sperm. It’s surprising to learn that Watson & Crick had published their model of DNA’s structure, opening the world of modern genetics, several years before the number of human chromosomes was firmly established!
Good things come in small packages
By the end of the 20th century, knowledge of DNA structure and the mechanisms of cell division had advanced dramatically. Yet, based on their school textbooks, most people still tended to picture chromosomes as the condensed “X-shaped” bodies seen in karyotypes. DNA was known to uncoil between cell divisions, but it was hard to imagine how such long straggling threads (more than 2 meters, or 6 feet, per cell) could pack into a nucleus only 6/1,000,000 of a meter in diameter (smaller than the diameter of a human hair).
Eventually, studies showed that DNA decreases in length when regions of about 166 base pairs wrap like twine around small proteins to form complexes known as nucleosomes . A short stretch of non-wound DNA falls between each nucleosomal unit, the result looking a bit like a string of beads. In such a configuration, a 1-meter (3-foot) strand of DNA is reduced to 14 cm (about 6 inches). This shortened strand then coils even more, until an X-shaped chromosome in a dividing cell measures roughly 1/10,000 the length of the DNA strand it contains!
The “fractal globule” (aka ramen noodles)
So what does the 3-dimensional model of the nucleus, as seen in the Genome Ball, have to do with all this?
One of the most important discoveries in genome biology has been the demonstration that genomes are non-randomly organized in the nucleus.
Even though chromatin looks like long straggly threads, it is amazingly well organized: Thanks to the organized coiling of chromatin, genes are able to interact with the DNA regions that regulate them.
The genome is organized into “distinct regions of open and closed chromatin regulatory domains,” explains Dr. Laura Elnitski, senior investigator at the National Human Genome Research Institute (NHGRI) of the National Institutes of Health. Put more simply, chromatin that is less active in a given cell type, or chromosomes containing few genes, are located just inside the nuclear membrane; but more active chromatin (for example, a gene coding for insulin in healthy pancreatic cells), and chromosomes carrying many genes, occupy the center of the nucleus. Overall, the nuclear location of specific genes correlates with their activity in a given cell.
Erez Aiden (who spearheaded the Genome Ball project) also discussed chromatin organization in his prize-winning essay in Science: “Loci on the same chromosome – even at opposite ends – interact more than loci on different chromosomes.” And within individual chromosomes, “open [active] chromatin interacts more with open chromatin and closed with closed,” wrote Aiden. In short: Genes have more interactions with regions on their own chromosome; and within any given chromosome, active regions group together with other active regions, while quiet or gene-poor areas group with other quiet regions.
Aiden had found a paper theorizing that long polymers – DNA is a good example – are able to form very tight coils with no knots, “a configuration known as the fractal globule.” One of the most striking characteristics of the fractal globule is that it can be folded and refolded without disturbing the rest of the condensed polymer.
The fractal globule is easy to explain to graduate students because it closely resembles the only food we can afford: ramen, said Aiden.
Uncooked, the noodles don’t contain any knots. Even when partially cooked, they don’t get tangled in the cooking pan. However, ramen noodles do become tangled after cooking, whereas chromatin stably maintains its unknotted state throughout interphase – the period between cell divisions when chromatin in the nucleus uncoils. In that condensed but non-knotted configuration, sections of chromatin that are far apart on the long strands may be brought into proximity. Thus, interactions between chromatin on the same chromosome, or between sections with similar properties or functions, are made possible by the way chromatin is organized in the interphase nucleus.
These are but a few of the innovative and complex understandings that inspired the creators of the Genome Ball (for more information about the 3-D printing of the Genome Ball displayed at the exhibition, see the feature article “Super 3D Model: How the Genome Ball Was Created” on this website). Our knowledge of the nucleus has come a long way in the 332 years since Leeuwenhoek. But, as Aiden’s Science essay concluded: “at the fringes of our maps the world is full of surprises.”
The same is certainly true of the nucleus.
Source: Unlockinglifescode.org/the-genome-ball. Access November 19, 2017, Genome Project NIH
(2) “DNA packaging: Nucleosomes and Chromatin.” Nature Education 1 (2008):26.
(3) “Regulatory and Epigenetic Landscapes of Mammalian Genomes,” Current Topics in Genome Analysis 2014. March 26, 2014.
(4) “Leeuwenhoek Sees the Cell Nucleus.” Science of Aging: Timeline of Discoveries.
(5) Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome. Science 326 (9 October 2009): 189-324.
Source: NIH (National Institute of Health) Genomic Project access and received for distribution 11/18/2017
Click on the link below:
We are all over this world in many countries, with differences, shades of color, opinions, thoughts. Make no mistake we are one, our ancestors came out of Africa. It’s in your DNA. I have found relatives in Brazil, India, Iran, Syria, Australia, Mexico, Boro Bora, Korea, China, and Japan. Never stop your journey finding your past. Gedmatch is a good place to start.
DNA collection, testing, and results are different for people of color and the algorithms used are not geared towards our DNA but can be very useful. It is Eurocentric, however, Helix, National Geo2, and 23andMe are moving towards a more inclusive model. Also, there are new projects in many countries to match DNA for people around the world.
Adult ADHD: An imbalance between the online and offline brain (https://www.genome.gov/27569602/2017-news-feature-adult-adhd-an-imbalance-between-the-online-and-offline-brain/?utm_source=NHGRI+Email+Updates&utm_campaign=5b96bdbf21-Skin+Pigmentation+publications&utm_medium=email&utm_term=0_3d227b0341-5b96bdbf21-118937769)
By Jeannine Mjoseth (mailto:Jeannine.Mjoseth@nih.gov)
November 7, 2017
A new study by researchers at the National Human Genome Institute (NHGRI) examined why some people grow out of childhood attention deficit hyperactivity disorder (ADHD), while others continue to have symptoms into adulthood. They discovered that adults with ADHD persisting from childhood partly lose the usual balance of connections between brain networks that control action and those that control daydreaming or introspecting. Researchers have argued that this imbalance – between the brain “online” and the brain “offline”- might account for the lapses of attention that are found in ADHD. By contrast, adults who had “grown out” of their childhood ADHD, did not show such a loss of balanced brain activity, according to findings published October 31, 2017, in The Proceedings of the National Academy of Science (PNAS).
“We hope to understand the mechanisms that explain why some people outgrow ADHD and other do not,” said Philip Shaw, B.M.B.Ch., Ph.D., senior author and an investigator in NHGRI’s Social and Behavioral Research Branch (https://www.genome.gov/11508935/Social-and-Behavioral-Research-Branch/Social-and-Behavioral-Research-Branch/Social-and-Behavioral-Research-Branch?utm_source=NHGRI+Email+Updates&utm_campaign=5b96bdbf21-Skin+Pigmentation+publications&utm_medium=email&utm_term=0_3d227b0341-5b96bdbf21-118937769) . “If we can understand why some people can recover from ADHD, we also might be able to apply this knowledge to other neuro-developmental conditions like learning disabilities or problems with social interaction.”
ADHD (https://www.nimh.nih.gov/health/topics/attention-deficit-hyperactivity-disorder-adhd/index.shtml?utm_source=NHGRI+Email+Updates&utm_campaign=5b96bdbf21-Skin+Pigmentation+publications&utm_medium=email&utm_term=0_3d227b0341-5b96bdbf21-118937769) is a heritable and treatable brain disorder marked by inattention and/or hyperactivity-impulsivity that can cause great difficulties with impulse control, attention span in school, social situations and the workplace. Around 20 to 30 percent of people with ADHD retain the full syndrome as young adults and about 50 percent show partial, though not complete remission.
The researchers looked at brain function in 205 adult participants: 101 participants had been diagnosed with childhood ADHD and 104 subjects never had ADHD. They looked at changes in the brain’s oxygen levels to determine the location of brain networks using functional magnetic resonance imaging (fMRI) (mailto:http://fmri.ucsd.edu/Research/whatisfmri.html) , and they studied the different levels of neuronal activity that by looking at the brain’s magnetic fields using magnetoencephalography (mailto:http://ilabs.washington.edu/what-magnetoencephalography-meg) .
Regardless of the type of brain imaging used, the researchers found that adults who had inattentive symptoms persisting from childhood lost the usual balance of connections between the online and offline brain networks. Specifically, a network that is prominent when a person is introspective is usually switched off when a person engages in tasks. This balance was partly lost in the adults with persistent inattention. By contrast, this pattern of connections between brain networks in adults who outgrew ADHD looked very similar to the adults who never had ADHD. These findings support the theory that among individuals who recover from ADHD, there is a childhood disruption to brain function that corrects itself by adulthood.
“Most adults have a balance between the online, task-oriented brain and the offline, day-dreaming brain, but we found that’s not the case for adults whose ADHD persists,” said Gustavo Sudre, Ph.D., study co-author and postdoctoral research fellow in Dr. Shaw’s lab. “We found that adults who recovered from ADHD had a very similar balance of online and offline brains to those who never had ADHD.”
NHGRI’s investment in this type of high impact, longitudinal research and the participants’ long-term commitment to ADHD research make studies like this possible.
“We first met these individuals at the National Institutes of Health Clinical Center when they were eight years old,” Dr. Shaw said. “They are so committed to ADHD research that they have kept coming back for 14 years. It’s great to see so many of the children who had severe ADHD grow into adults who are managing very well.”
In the next step of their research, Drs. Shaw and Gustavo will collaborate with an international ADHD research consortium to find genes associated with the disrupted brain networks.
Read the study
Sudre G, Szekely E, Sharp W, Kasparek S, Shaw P. Multimodal mapping of the brain’s functional connectivity and the adult outcome of attention deficit hyperactivity disorder (http://www.pnas.org/content/114/44/11787.full?utm_source=NHGRI+Email+Updates&utm_campaign=5b96bdbf21-Skin+Pigmentation+publications&utm_medium=email&utm_term=0_3d227b0341-5b96bdbf21-118937769) . PNAS, October 31, 2017.
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How to Check Genesis.Gedmatch.com for African Royal DNA Project Matches
October 11, 2017
Note: Any problems understanding to procedures or questions please directed to me or RoyalDNA@DNATestedAfricans.org
*Great website with a ton of information, highly recommended.
Here’s a workable solution to help you check to see if you match any African Royal DNA Project Kits. Because there are so many of you, we cannot compare your DNA for you all. This is the quickest way to check for yourself to see if you match any of the kits we manage. You MUST follow these steps prior to contacting us about the potential DNA match. This also helps YOU to learn how too use the FREE tools.
PLEASE REMEMBER THAT WE DO NOT POST GEDMATCH OR GENESIS KIT NUMBERS IN ANY SOCIAL MEDIA. SHARING THE GEDMATCH ON GENESIS NUMBERS IN ANY FORUM, WILL RESULTS IN PERMANENT REMOVAL FOR ALL GROUPS AND PROGRAMS. PRIVACY AND SAFETY IS MOST IMPORTANT. THIS INCLUDES FTDNA KIT #S AND ANY KIT # THAT YOU RECEIVE REGARDING YOUR ANCESTRY AND DNA UPLOADS. When sending emails to your Gedmatch and / or Genesis matches, send one email per person. That is their rule. No mass emails. If you are caught, Gedmatch may delete your data and you lose access.
Register at this link https://genesis.gedmatch.com/ if you have not done so. If you register and get a notice that the email you are using already exists, simply log into the link with your Gedmatch.com log in credentials. (Please read the website first before making a decision to upload your DNA Raw data)
Upload your DNA Raw Data. It may take a day or 2 for your matches to populate.
If any African Royal appears on your match list, you MUST complete the one to one comparison. The CMs must be at least 7 and the SNPs must be at least 700 to be a CONFIRMED match. Click on your Genesis kit #. You will see a list of matches. You are almost there!
If you do not see them on your list, you are not a match. Their names are distinctive and includes ethnic group(s) and they will include their ethnic groups(s).
If you see any of the Royals’ names there, click on the letter “A” beside their name . This will allow you to do a one to one comparison.
The one to one comparison will show the chromosomes that you match on .
The above image shows 4 rows of matching for Chromosome 1. The Centimorgans (CMs) on 1 row MUST be at least 7 and the the SNPs must be 700. You cannot add up all of them to meet this requirement
The image below shows on row 1 that this match has 47.2 CMs and 6,993 SNPs. That means they are a legitimate match.
If the above requirements are met, copy the chromosome details that you match on and draft an email to RoyaLDNA@DNATestedAfricans.org . Paste the info in the email .
We will then provide you with contact Info for your DNA match if they provided it to us.
Here is the template to use for the email https://www.dnatestedafricans.org/single-post/2017/10/01/How-to-Email-Your-New-DNA-Matches
See our DNA Tested African Descendants group guidelines http://goo.gl/forms/Om5AqGGahm
For some time now I have talked about the impact of slavery in any form against any ethnic group or person has profound consequences. Impact of child abuse over a long period of time, sexual assault carries a burden that we are just beginning to understand. This article is one of those must-read articles.
NIH completes atlas of human DNA differences that influence gene expression
Bethesda, Md., Wed., Oct.11, 2017 – Researchers funded by the National Institutes of Health (NIH) have completed a detailed atlas documenting the stretches of human DNA that influence gene expression – a key way in which a person’s genome gives rise to an observable trait, like hair color or disease risk. This atlas is a critical resource for the scientific community interested in how individual genomic variation leads to biological differences, like healthy and diseased states, across human tissues and cell types.
The atlas is the culmination of work from the Genotype-Tissue Expression (GTEx) Consortium, established to catalog how genomic variation influences how genes are turned off and on.
“GTEx was unique because its researchers explored how genomic variation affects the expression of genes in individual tissues, across many individuals, and even within an individual,” said Simona Volpi, Ph.D. , program director for GTEx at the National Human Genome Research Institute (NHGRI), who oversaw various parts of the project.
According to Dr. Volpi, there was previously no resource at the scale used by GTEx that enabled researchers to study how gene expression in the liver might be different than in the lung or heart, for example, and how those differences relate to the inherited genomic variation in an individual.
Researchers involved in the GTEx Consortium collected data from more than 53 different tissue types (including brain, liver and lung) from autopsy, organ donation and tissue transplant programs. These tissues came from a approximately 960 donors in total.
“GTEx depended entirely on families choosing to donate biosamples for research after the death of a loved one,” said Susan Koester, Ph.D., deputy director for the Division of Neuroscience and Basic Behavioral Science and GTEx program director at the National Institute of Mental Health (NIMH). “GTEx researchers are deeply grateful for this priceless gift.”
The project continues to house a biobank of collected tissue samples, as well as extracted DNA and RNA for future studies by independent researchers. The summary-level data are available to the public through the GTEx Portal, and the most recent release of the raw data has been submitted to the Database of Genotypes and Phenotypes (dbGaP), an archive of results from studies that investigate the genomic contributions to phenotypes (physical characteristics or disease states).
GTEx launched in 2010 and concluded in the summer of 2017. It was supported by the NIH Common Fund and administered by NHGRI, NIMH and the National Cancer Institute (NCI), all part of NIH.
As one example of how the atlas can be used, a new study published online in the journal Nature, describes the results of expression quantitative trait locus (eQTL) mapping in 44 different human tissues from 449 individuals. An eQTL is a small section of the genome that contributes to the differences in gene expression between genes and between individuals. Typically, eQTLs are identified by sequencing the genomes of genetically different individuals to determine the variation in the genome between those individuals. This is followed by determining how much each gene is being expressed. Lastly, the eQTLs are identified by establishing which specific variants are associated with differences in gene expression levels.
The authors of the study used GTEx data to catalog all known eQTLs in the human genome for the first time. As in the Nature study, GTEx data will help researchers understand the mechanisms of how genes are expressed in a variety of tissues, which will ultimately better inform our knowledge of how genes are mis-regulated in the context of disease. GTEx data can also be used to better understand the variations in gene expression that underlie differences among healthy individuals.
Although the GTEx project has officially wrapped up, plans for future work are already underway. An endeavor known as the Enhancing GTEx (eGTEx) project, which began in 2013, extends GTEx’s efforts by combining gene expression studies with additional measurements, such as protein expression. This work is being conducted on the same tissues as in the GTEx project, providing a richer resource that integrates the complexity of how our genomes function in biologically meaningful ways.
Read the studies:
Aguet et al. Genetic effects on gene expression across human tissues. Nature, doi:10.1038/nature24277. 2017. [Full Text]
Stranger et al. Enhancing GTEx by bridging the gaps between genotype, gene expression, and disease: The eGTEx project. Nature Genetics, DOI: 10.1038/ng.3969. 2017. [Full Text]
NHGRI is devoted to advancing health through genome research. The institute led NIH’s contribution to the Human Genome Project, which was successfully completed in 2003 ahead of schedule and under budget. Building on the foundation laid by the sequencing of the human genome, NHGRI’s work now encompasses a broad range of research aimed at expanding understanding of human biology and improving human health. In addition, a critical part of NHGRI’s mission continues to be the study of the ethical, legal and social implications of genome research. Additional information about NHGRI can be found at: www.genome.gov.
About the National Institute of Mental Health (NIMH): The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.
About the National Cancer Institute (NCI): NCI leads the National Cancer Program and the NIH’s efforts to dramatically reduce the prevalence of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI website at cancer.gov or call NCI’s Cancer Information Service at 1-800-4-CANCER.
The NIH Common Fund encourages collaboration and supports a series of exceptionally high-impact, trans-NIH programs. Common Fund programs are designed to pursue major opportunities and gaps in biomedical research that no single NIH institute could tackle alone, but that the agency as a whole can address to make the biggest impact possible on the progress of medical research. Additional information about the NIH Common Fund can be found at http://commonfund.nih.gov.
About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
Posted: October 11, 2017