scholarly journals Folate Deficiency Triggers the Abnormal Segregation of a Region With Large Cluster of CG-Rich Trinucleotide Repeats on Human Chromosome 2

2021 ◽  
Vol 12 ◽  
Author(s):  
Lorenza Garribba ◽  
Ivan Vogel ◽  
Mads Lerdrup ◽  
Marisa M. Gonçalves Dinis ◽  
Liqun Ren ◽  
...  
Keyword(s):  
Human Chromosome ◽  
Trinucleotide Repeat ◽  
Folate Deficiency ◽  
Fragile Sites ◽  
Human Cells ◽  
Chromosome 2 ◽  
Genome Database ◽  
Human Disorders ◽  
New Evidence

Folate deficiency is associated with a broad range of human disorders, including anemia, fetal neural tube defects, age-associated dementia and several types of cancer. It is well established that a subgroup of rare fragile sites (RFSs) containing expanded CGG trinucleotide repeat (TNR) sequences display instability when cells are deprived of folate. However, given that folate sensitive RFSs exist in a very small percentage of the population, they are unlikely to be the cause of the widespread health problems associated with folate deficiency. We hypothesized that folate deficiency could specifically affect DNA replication at regions containing CG-rich repeat sequences. For this, we identified a region on human chromosome 2 (Chr2) comprising more than 300 CG-rich TNRs (termed “FOLD1”) by examining the human genome database. Via the analysis of chromosome shape and segregation in mitosis, we demonstrate that, when human cells are cultured under folate stress conditions, Chr2 is prone to display a “kink” or “bending” at FOLD1 in metaphase and nondisjunction in anaphase. Furthermore, long-term folate deprivation causes Chr2 aneuploidy. Our results provide new evidence on the abnormalities folate deficiency could cause in human cells. This could facilitate future studies on the deleterious health conditions associated with folate deficiency.

scholarly journals Folate deficiency drives mitotic missegregation of the human FRAXA locus

2018 ◽  
Vol 115 (51) ◽  
pp. 13003-13008 ◽  
Author(s):  
Victoria A. Bjerregaard ◽  
Lorenza Garribba ◽  
Cynthia T. McMurray ◽  
Ian D. Hickson ◽  
Ying Liu
Keyword(s):  
Trinucleotide Repeat ◽  
Fragile X ◽  
Chromosome Instability ◽  
Extended Period ◽  
Folate Deficiency ◽  
Causative Factor ◽  
Repeat Sequence ◽  
Fragile Sites ◽  
Chromosome X ◽  
Mitotic Abnormalities

The instability of chromosome fragile sites is implicated as a causative factor in several human diseases, including cancer [for common fragile sites (CFSs)] and neurological disorders [for rare fragile sites (RFSs)]. Previous studies have indicated that problems arising during DNA replication are the underlying source of this instability. Although the role of replication stress in promoting instability at CFSs is well documented, much less is known about how the fragility of RFSs arises. Many RFSs, as exemplified by expansion of a CGG trinucleotide repeat sequence in the fragile X syndrome-associated FRAXA locus, exhibit fragility in response to folate deficiency or other forms of “folate stress.” We hypothesized that such folate stress, through disturbing the replication program within the pathologically expanded repeats within FRAXA, would lead to mitotic abnormalities that exacerbate locus instability. Here, we show that folate stress leads to a dramatic increase in missegregation of FRAXA coupled with the formation of single-stranded DNA bridges in anaphase and micronuclei that contain the FRAXA locus. Moreover, chromosome X aneuploidy is seen when these cells are exposed to folate deficiency for an extended period. We propose that problematic FRAXA replication during interphase leads to a failure to disjoin the sister chromatids during anaphase. This generates further instability not only at FRAXA itself but also of chromosome X. These data have wider implications for the effects of folate deficiency on chromosome instability in human cells.

scholarly journals In utero cell transfer between porcine littermates

2011 ◽  
Vol 23 (2) ◽  
pp. 297 ◽  
Author(s):  
Andrea McConico ◽  
Kim Butters ◽  
Karen Lien ◽  
Bruce Knudsen ◽  
Xiaosheng Wu ◽  
...  
Keyword(s):  
Immune System ◽  
Cord Blood ◽  
Normal Pregnancy ◽  
Human Cells ◽  
Cell Transfer ◽  
System Function ◽  
Human Cord Blood ◽  
Immune System Function ◽  
Vascular Connections

Trafficking of cells between mother and fetus during the course of normal pregnancy is well documented. Similarly, cells are known to travel between twins that share either a placenta (i.e. monozygotic) or associated chorion (i.e. monochorionic). Transferred cells are thought to be channelled via the vessels of the placenta or vascular connections established via the chorion and the long-term presence of these cells (i.e. microchimerism) can have important consequences for immune system function and reparative capacity of the host. Whether cells can be transferred between twins with separate placentas and separate chorions (i.e. no vascular connections between placentas) has not been investigated nor have the biological consequences of such a transfer. In the present study, we tested the possibility of this type of cell transfer by injecting human cord blood-derived cells into a portion of the littermates of swine and probing for human cells in the blood and tissues of unmanipulated littermates. Human cells were detected in the blood of 78% of unmanipulated littermates. Human cells were also detected in various tissues of the unmanipulated littermates, including kidney (56%), spleen (33%), thymus (11%) and heart (22%). Human cells were maintained in the blood until the piglets were sacrificed (8 months after birth), suggesting the establishment of long-term microchimerism. Our findings show that the transfer of cells between fetuses with separate placentas and separate chorions is significant and thus such twins may be subject to the same consequences of microchimerism as monozygotic or monochorionic counterparts.

Human chromosome 2 rod/ring mosaicism: probable origin by prezygotic breakage and intrachromosomal exchange

1982 ◽  
Vol 33 (3) ◽  
pp. 222-231 ◽  
Author(s):  
H.E. Wyandt ◽  
R. Kasprzak ◽  
A. Lamb ◽  
K. Willson ◽  
W.G. Wilson ◽  
...  
Keyword(s):  
Human Chromosome ◽  
Chromosome 2 ◽  
Probable Origin

Assignment of the T-cell differentiation gene MAL to human chromosome 2, region cen?q13

1988 ◽  
Vol 27 (2) ◽  
pp. 91-95 ◽  
Author(s):  
Miguel A. Alonso ◽  
David E. Barton ◽  
Uta Francke
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Human Chromosome ◽  
T Cell Differentiation ◽  
Chromosome 2 ◽  
Differentiation Gene

scholarly journals Supporting the development of scientific understanding when constructing an evolving explanation

2022 ◽  
Vol 4 (1) ◽  
Author(s):  
Ann M. Novak ◽  
David F. Treagust
Keyword(s):  
Scientific Explanation ◽  
Project Based Learning ◽  
Incremental Development ◽  
Freshwater Organisms ◽  
Freshwater System ◽  
New Evidence ◽  
Scientific Ideas ◽  
Over Time

AbstractWe explore how students developed an integrated understanding of scientific ideas and how they applied their understandings in new situations. We examine the incremental development of 7th grade students’ scientific ideas across four iterations of a scientific explanation related to a freshwater system. We demonstrate that knowing how to make use of scientific ideas to explain phenomena needs to be learned just as developing integrated understanding of scientific ideas needs to be learned. Students participated in an open-ended, long-term project-based learning unit, constructing one explanation over time to address, “How healthy is our stream for freshwater organisms and how do our actions on land potentially impact the water quality of the stream?” The explanation developed over several weeks as new data were collected and analyzed. Students discussed evidence by revisiting scientific ideas and including new scientific ideas. This research investigates two questions: (1) As students engage in writing a scientific explanation over time, to what extent do they develop integrated understanding of appropriate scientific ideas? and (2) When writing about new evidence, do these earlier experiences of writing explanations enable students to make use of new scientific ideas in more sophisticated ways? In other words, do earlier experiences allow students to know how to make use of their ideas in these new situations? The results indicated statistically significant effects. Through various iterations of the explanation students included richer discussion using appropriate scientific ideas. Students were also able to make better use of new knowledge in new situations.

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