FAQ - chromosome fragility
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If a woman 5 months pregnant just found out her baby has an extra chromosome what does this mean?

I don't know specifically, I know nothing about this stuff. I jsut know she just found out there was an extra chromosome. And alos the baby has a heart defect and may be down syndrome. Are there all different types of extra chromosome defects?

Yeah there can be different chromosomes that are affected. It depends which one is there an extra of. Heres some examples I got off a sight. Hope that helps out and hope everything turns out fine. My prayers are with you!

The perfect number of chromosomes for humans is 46. We have 46 chromosomes in almost
all of our cells - that is, 22 pairs of autosomes, numbered 1 through 22, plus the two
sex chromosomes, called X and Y. Normally, females contain two X chromosomes in their
cells in addition to the 44 autosomes. We describe female chromosomes as 46,XX (46
including 2 X' s). The cells of a male contain an X chromosome and a Y chromosome plus
44 autosomes; we describe their chromosomes as 46,XY.
Can a person survive with too many or too few chromosomes? Since the chromosomes contain
genes that are needed for our growth and development, it makes sense that we cannot grow
and develop successfully if any chromosomes are missing.

Only in the case of the X chromosome is it possible for a person to survive with a missing
chromosome, even though the X chromosome is a fairly large chromosome. Considering that a
normal, healthy male can manage with only one X chromosome (and a Y, of course), it is not
surprising that a woman with only one X chromosome may be able to survive at all.

A person with only one sex chromosome, an X, will be a female with Turner syndrome,
perhaps the mildest of all the chromosome abnormalities. We describe her chromosomes
as 45,X (meaning that each cell contains 45 chromosomes, including one X chromosome).
Even with Turner syndrome, most pregnancies will not continue to term but will end in
a miscarriage - only some will survive. The symptoms of Turner syndrome are quite
significant for those who have to live with them.

A person with only one Y chromsome (45,Y) could not survive or be born alive. The X
chromsome ahs important genes on it that would be completely missing in such a person.

As to why it is harmful to have an extra chromosome, this is harder to understand. If
chromosomes are good, wouldn't additional chromosomes be even better? The answer is no,
they would not. The genes on the chromosomes are needed in exactly the correct amount in
order to work correctly. (As with medicine, you need the right dose!)

Many genes cause the cell to make proteins of various kinds, and these are needed in the
correct amounts. Some genes function by instructing other genes to turn on and off at the
right moment, and these instructions need to be precise, accurate and sensitive. Having an
extra chromosome is like having a business with too many managers or a family with too
many parents or a car with two drivers or a country with two presidents, perhaps giving
contradictory instructions.

The smallest of all the chromosomes is chromosome 21. A person who has, not two but three
copies of chromosome 21 has Down syndrome, a well-known form of mental retardation.

Are people ever found with other extra chromosomes besides chromosome 21? Hardly ever.
Those babies who are born with extra copies of larger chromosomes may not survive for
long; they have many different health problems and birth defects.

Once again, the exception is the sex chromosomes. It is possible for males to survive with
two Y chromosomes (47, XYY instead of 46, XY). It is also possible to survive with an
extra X chromosome - 47, XXX females (triple-X syndrome) and 47, XXY males (Klinefelter
syndrome).  (+ info)

Does Crohn's Disease have an extra chromosome or a loss of a chromosome?

If it does which chromosome number does it occur in in?

No, experts don't really know the cause(s) of Crohn's disease. It is simply an inflammatory bowel disease. Some believe it is can be caused when the immune system has an abnormal response to normal bacteria in the intestines, (an autoimmune disorder.) It also seems to run in families but there is no missing or extra chromosome involved.  (+ info)

What chromosome is diabetes linked to?

I need to know for type 1 and 2 and gestational diabetes.

it is not linked to a chromosome  (+ info)

How did he 1st chromosome ever come to be.?

If something came from nothing HOW?
How do evolutionist explain the arrival of the first chromosome since the probability is 1 in 9 trillion?

Magic.  (+ info)

what is the gene or chromosome info for dwarfism?

also what type of diseaese is it single gene, chromosomal, or is it mitochondrtial?

Mutations in the SLC26A2 and COL2A1 genes cause achondrogenesis types 1B and 2, respectively. The genetic cause of achondrogenesis type 1A is unknown. Achondrogenesis, also known as dwarfism.

Achondrogenesis type 1B is the most severe skeletal disorder caused by mutations in the SLC26A2 gene. This gene provides instructions for making a protein that is essential for the normal development of cartilage and for its conversion to bone. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Mutations in the SLC26A2 gene disrupt the structure of developing cartilage, preventing bones from forming properly and resulting in the skeletal problems characteristic of achondrogenesis type 1B.

Achondrogenesis type 2 is one of several skeletal disorders that result from mutations in the COL2A1 gene. This gene provides instructions for making a protein that forms type II collagen. This type of collagen is found mostly in cartilage and in the clear gel that fills the eyeball (the vitreous). It is essential for the normal development of bones and other tissues that form the body's supportive framework (connective tissues). Mutations in the COL2A1 gene interfere with the assembly of type II collagen molecules, which prevents bones and other connective tissues from developing properly.  (+ info)

My wife had a miscarriage in july 2007. Her doctor explained that it was due to a chromosome issue?

The doctor explained that each parent has 23 chromosomes to make up 46 chromosomes etc... This didn't happen. My question is that my wife is pregnant again and we would like to know what the chances of this happening again are. She took the pregnancy test and her period was due Oct 31, 2007. The test came up positive. We just don't want to go through this again because it was painful for both of us mentally and it was very painful for my wife physically.

I'm so sorry for you loss (I lost a baby when I was seven months pregnant). Don't dwell on what happened - dwell on what could happen! There is know way you can no the future... but enjoy the here and now and what's meant to be will be. I agree with the other answerers here too - seek more information from your doctor. Good luck and best wishes!  (+ info)

How long does it take to test for chromosome numbers 7 and 15?

Overview of Chromosome 7 Project
Objectives of the project
Introduction to human chromosome 7
Progess of the project



The goal of the human genome project is to identify all the genes in the human genome. A complete map of human chromosomes is a crucial component in studying human genetics and biology, and for understanding the normal function of genes as well as disease conditions. The overall objective of our CGAT-funded research program has been to construct a combined physical, genetic, and transcription map of the long arm of chromosome 7 (7q). Our secondary goals are to develop new mapping technologies and to use our mapping data to begin to study disease conditions and the breakpoints in common chromosome rearrangements. The primary strategy of our approach is based on the construction of overlapping contigs of high quality yeast artificial chromosome (YAC) clones selected from a chromosome 7-specific library made in our laboratory.

While a long range physical map is an important frame of reference in genome research, its utility will be maximized by the identification and localization of all the transcription units in each of the defined chromosome regions. The information will be an integral part of the human genome project. A detailed characterization of each of the transcription units will not only serve as the basis for studies of the structure and organization of the human genome, but will also provide important insights into the regulatory mechanisms of gene expression and human biology. Key biological consequences relating to expression nuances resulting from longer range structural differences may contribute to variation or phenotypic differences during development and aging processes of normal and disease states. Further, candidate genes will be immediately applicable to positional cloning studies on genetic diseases. The specific aims of our project are:

To complete the physical map for 7q by YAC contig construction and fill the gaps between existing contigs by alternative strategies;

To assemble a minimally essential physical map for 7p by the YAC contig strategy;

To continue to localize all published and unpublished DNA and gene segments (including sequence tag sites and expressed sequence tags), as well as available genetic markers;

To isolate, characterize and map all the transcribed sequences on 7q;

To perform large scale DNA sequencing for selected regions on 7q; and

To implement a public chromosome 7 database and upgrade local capability in bioinformatics.


Chromosome 7 accounts for approximately 5% of the human genome and it is estimated to be 136 centiMorgans (cM) in length and contain 170 million bp (170 Mb) of DNA. The chromosome is noted by its distinct light and dark band patterns upon Giemsa-staining. Since these characteristics are generally believed to be associated with gene-rich and gene-poor regions, respectively, there may be an unusual spatial distribution of genes and repetitive elements on this chromosome. There are more than 190 genes or gene-like sequences listed in the Genome Database for this chromosome as well as 2,502 DNA segments, a large portion of which were contributed by our laboratory. Assuming a total of 50,000-70,000 genes in the human genome [1], chromosome 7 should contain 3,000-3,500 genes, 2/3 of which are expected to be on 7q. There are more than 25 disease gene loci identified on chromosome 7 [reviewed in ref. 2 and 3]. Only about half of them have been characterized at the molecular level, due to either prior knowledge of biochemical defects or positional cloning on the basis of genetic mapping. The others are congenital abnormalities defined by specific chromosome 7 rearrangements. Chromosome 7 abnormalities have also been implicated in many cancer conditions, including acute non-lymphocytic leukemia or myelodysplastic syndrome, ataxia telangiectasia, erythroleukemia, gamma heavy chain disease, primary breast cancer, ovarian cancer, heritable non-polyposis colorectal cancer, lung carcinoid tumor, prostate carcinoma, transitional cell carcinoma of ureter, bilateral renal oncocytoma, malignant melanoma, epidermal carcinoma, pancreatic carcinoma, glioblastoma, and some forms of chronic T lymphocyte tumors. It is also of interest to note that chromosome 7 is particularly unstable and vulnerable to breakage in cell culture studies.


1. To refine and improve our chromosome 7-specific library

The chromosome 7-specific YAC library which has been used as the basis of our mapping strategy was constructed with DNA from somatic cell hybrids containing a single human chromosome 7. We have continued to isolate recombinant clones containing human sequences by hybridization with radioactively labeled total human DNA as probe. To date, we have isolated 1,700 clones from this chromosome 7-specific library, each with an average insert size of 520 kb and with the proportion of chimeric clones being less than 10%. The clones are individually stored in glycerol vials as well as 96-well trays. They have been distributed freely to all interested laboratories. We have also enriched our coverage of the chromosome by isolating additional 3,464 clones from the total human genomic YAC libraries constructed by CEPH, the Imperial Cancer Research Fund (ICRF), Medical Research Council (the ICI library) and ourselves (the NCE library). While many of the latter clones were retrieved from the CEPH library based on the published information from Genethon [27], others were isolated by screening with chromosome 7-specific probes. The combined collection thus represents a coverage of 5-10 genome equivalents for this chromosome (less for 7p).

2. To group YAC clones according to chromosome regions

Two strategies have been used to place the individual YAC clones to defined cytogenetic intervals; they are (a) hybridization-screening with existing DNA segments that are already regionally mapped and (b) direct fluorescence in situ hybridization (FISH). Including the DNA and gene segments that were available to us at the beginning of our study, we have accumulated to date 817 DNA markers, each of which has been mapped with our somatic cell hybrid panel to one of 20 intervals along 7q. These markers include 106 gene segments, 164 microsatellite markers from Genethon, 30 from the Cooperative Human Linkage Center, 44 from Utah, 12 from Eurogem, 150 expressed sequence tags (ESTs), and 311 arbitrary DNA segments and sequence tag sites (STSs). This screening has identified a total of 2,443 YAC clones. Greater than 90% of the probes used have been found to detect at least one YAC clone (and in most cases 2 or more clones) already identified by one or more other probes. Moreover, since all the probes have been regionally mapped, the identified YAC clones are automatically groups according to the cytogenetic intervals. The chromosome locations for 651 YAC clones have also been obtained by FISH analysis. While the latter mapping technique has confirmed or refined the localization for most clones, we have also obtained new mapping information for over 50 clones. Thus, the combined mapping strategy has permitted the integration of all genetic, physical, and gene maps into a single consensus map.

3. To identify overlapping YAC contigs

As a built-in feature of our DNA marker screening strategy, overlapping YAC contigs are assembled as clones are identified. In addition, contigs have been linked and oriented by using the "fingerprinting" and Alu-PCR hybridization techniques, and by chromosomal walking with probes derived from ends of contigs. Using a combination of these two approaches, we have constructed a minimally overlapping set (minimal tiling path) of 341 YAC clones that contain the cytogenetic localization information and relative order of 500 DNA markers for 7q, the boundaries of which are defined by a set of YAC clones mapping to the centromere of the chromosome and a clone containing the true telomeric end of 7qter (from H. Donis-Keller of Washington University at St. Louis). Refined map locations for 317 markers have also been obtained by high resolution contig assembly for several chromosome regions. It is important to note that the YAC clones chosen for the tiling path are confirmed to be non-chimeric and to map to a single location on 7q by FISH. Further, since many of our DNA markers are obtained from the literature and databases at the MIT/Whitehead Institute Genome Center and Genethon, we have been able to compare and incorporate our integrated map with those publicly available ones.

Based on the results of our DNA marker screening and the sizes of YAC clones, we estimate that over 90% of 7q are covered by our YAC contigs at a resolution of 1 marker per 130 kb. Our mapping study, however, has identified 17 problematic regions in the YAC contig map. These "gaps" can be divided into 3 general categories, namely, those regions where genomic sequences are not present in any YAC libraries, those that are present but unstable as YACs, and those regions devoid of DNA markers (discussed in more detail below). Our subsequent chromosomal-walking studies indicate that the majority of the gap regions can be filled by bacterial-based cloning systems; for example, 29 of the 32 DNA markers not found in the YAC libraries could be identified in one or both of the flow-sorted human chromosome 7 cosmid library (from Lawrence Livermore National Laboratory) and the P1-based (PAC) library (from Pieter de Jong at Roswell Park Cancer Institute in Buffalo). Thus far, 753 cosmids and 140 PACs have been isolated in an attempt to cover the problematic regions and overlapping contigs are being assembled.

4. To construct a detailed physical map of the 7q21-q22 region

The 7q21-q22 region is the first chosen to be mapped in fine details because it contains a high density of chromosome breakpoints found in various disease conditions. Using a panel of somatic cell hybrids, we have refined the localization of 270 DNA markers and 30 genes, to 13 intervals in the q21-q22 region. The DNA markers in turn have identified 343 YACs that could be grouped into 4 large contigs (the largest covering 12 Mb) covering the vast majority of the estimated 30 Mb region. Concurrently, all the breakpoints of rearrangement contained in the somatic cell hybrid lines could be defined by flanking probes within YAC contigs. The fidelity of the YAC map and the total size of the region is being examined by using the free chromatin mapping technique (see below) as well as by construction of a long range restriction map with pulsed-field gel electrophoresis. Moreover, a set of YAC clones representing a minimal tiling path for 7q21-q22 has been used for direct cDNA selection experiments (see below).

The extent of overlap of YACs within the contigs has been assessed by DNA marker content, size of the YAC clones, Alu-PCR hybridization, and DNA fingerprinting experiments. For the q21-q22 region, the combination of all of these data has resulted in a reasonable estimation of the size of the contig map. It is calculated that the contigs cover 24 Mb of DNA. If the sizes of the small contigs in the gaps are added, the total length of the contigs spanning 7q21-q22 will be 26 Mb. This value is in good agreement with the size estimate (30 Mb) based on cytogenetic measurements. Then, it follows that the total length of gaps remained to be filled in this region may be as large as 4 Mb.

5. To apply and extend the utility of the free chromatin FISH for mapping YAC contigs

In addition to establishing general FISH mapping protocols in our laboratory, we have introduced a number of significant improvements. By controlling the denaturation time, we have greatly simplified the DAPI-staining procedure for easy mapping of FISH signals to chromosome bands. While FISH mapping of genomic phage, cosmid, and YAC clones is now routine, we have also been able to map small cDNA clones (<2 kb) by incorporation of several modifications, one of which is self-ligation of hybridization probes [28]. We have also employed our novel "free chromatin mapping" FISH analysis [29] to determine the order and organization of several genomic regions. Our data show that one of the gaps in the 7q21-q22 YAC contig map is only about 100 kb in size. The resolution of this procedure is estimated to be around 10 kb. Correlation with physical distance and map order could also be demonstrated for probes 1-2 Mb apart.

6. To identify transcribed sequences within large cosmid or YAC contigs

Using our mapping resources and the established cosmid and YAC contigs, we have used 3 strategies to assign and identify transcribed sequences (genes) on chromosome 7. First, the locations of 106 previously cloned or known genes have been determined or refined through hybridization or PCR screening with specific cDNA probes or STSs (or both) against the somatic cell hybrid mapping panel or YAC clones. Thus, these genes, previously mapped to only chromosome regions, are now localized to physical intervals on our YAC contigs. In the second strategy, we have obtained the sequences of all available EST from colleagues or public databases, synthesized PCR primers for each, and assigned each of them to our YAC contigs. Over 150 such ESTs have been mapped to date.

Our third strategy involves the identification of "new" genes. As one of our specific aims, we have proposed to develop state-of-the-art technology based on cDNA selection for gene discovery [21, 22], and to apply it to large cloned contigs of 7q. In brief, 15 primary libraries of cDNA have been constructed with RNA from cell lines, and tissues and major body organs of fetal and adult stages. The cDNA libraries are prepared with unique sequence tags which allow easily identification of the original tissue source. The information has been useful in isolation of full length cDNA clones from conventional libraries. The detailed procedures, sample applications, and assessment of the strategy have recently been published. The largest genomic region for which a systematic cDNA selection approach has been applied in our study corresponds to a minimal tiling path of 53 YAC clones that span a 30 Mb region of DNA at 7q21-q22. Smaller regions correspond to the YAC or cosmid clones that encompass the critical region for 10 different disease loci of interest. In total, over 50 selection experiments have been performed, and pools of cloned cDNA fragments generated from single as well as overlapping groups of YACs and cosmids from different genomic regions. Thus far, >400 unique cDNA clones have been isolated and their physical origins confirmed on the starting genomic clones. The clones are then grouped into transcription units by RNA hybridization and screening of conventional cDNA libraries with large inserts. Finally, DNA sequencing analysis and database search are performed to establish the identity of each clone.

7. To establish reference YACs and cosmids for cytogenetic analysis by FISH

To facilitate cytogenetic analysis of translocations and deletions involving chromosome 7, we have established an ordered set of 95 chromosome 7-specific YAC and 60 cosmid clones that are evenly spaced on 7q (Fig. 10). Each of the clones has been selected on the basis of its reliability as FISH probe and its single localization on chromosome 7. These clones cover a total of 60% of the chromosome. In addition to their application in mapping of disease genes (see below), some of the selected probes have also been applied in clinical diagnosis such as split hand/split foot malformation [30], Williams syndrome [31], and Smith-Laemli-Opitz Syndrome [32].

Chromosome 15 Duplications: Idic(15) and Interstitial Duplications
The duplication 15q Syndrome
by N. Carolyn Schanen, M.D., Ph.D.

This paper was presented by Dr. Schanen at the 2005 IDEAS Conference. Dr. Schanen is the Head of Human Genetics Research for Nemours Biomedical Research. She sits on the professional advisory board for IDEAS.

What is isodicentric 15?

Isodicentric chromosome 15 is the scientific name for a specific type of chromosome abnormality. Individuals with isodicentric chromosome 15, or "idic(15)", have 47 chromosomes instead of the typical 46 chromosomes. Occasionally, a person may have 2 extra idic(15) pieces(48 chromosomes) or 3 extra idic(15) pieces(49 chromosomes) in all or some of their cells. It is the presence of this extra genetic material that is thought to account for the symptoms seen in some people with idic(15). The extra chromosome is made up of a portion of chromosome 15 that has been duplicated and "inverted," so that there are two identical copies attached to one another that appear to be mirror images. Because of this arrangement, idic(15) used to be referred to as "inverted duplication chromosome 15." Most commonly, the region called 15q11-q13 is the portion of chromosome 15 duplicated. Sometimes the duplicated region is larger. The size of the idic(15) varies depending on the size of the region of chromosome 15 that is duplicated.

Individuals with idic(15) usually have a total of four copies of this chromosome 15 region instead of the typical two copies (1 copy each on the maternal and paternal chromosomes and 2 copies on the idic(15)). Some children and adults with idic(15) are said to have 'mosaicism', meaning that their extra 15th chromosome is present in some, but not all, of their body cells. Mosaicism occurs by chance in this and many other chromosomal disorders.

What is interstitial duplication 15?

People born without an extra chromosome but who have a segment of duplicated material within chromosome 15 are said to have an interstitial duplication. Most often this is the same section (15q11-13) that makes up the extra chromosome in idic(15). For this reason, people with interstitial duplications of 15q and those with idic(15) share similar characteristics. For both conditions, there is a wide range of severity from one person to the next; as a group however, people with interstitial duplication 15 tend to have milder symptoms than those with idic(15).

Generally, people with duplications of chromosome 15q do not have family members with the chromosome abnormality. The duplication usually forms by chance in one person in the family. Children with chromosome 15q duplications are born to parents of every socioeconomic, racial, and ethnic background. There is no known link between chromosome 15q duplications and environmental or lifestyle factors. In other words, there is nothing that parents did before or during pregnancy to cause their child to be born with a duplication of chromosome 15.

How common are duplications of chromosome 15?

Several types of studies have been done to address this question. First, population studies have been done to examine the frequency of extra chromosomes, often called marker chromosomes, in newborns. Based on those studies, 1 in 8000 people carry an extra chromosome that came from chromosome 15. The most common type of marker chromosome 15 is tiny and contains few active genes, thus they do not usually cause any problems and are only identified incidentally when chromosome testing is done for other reasons1. In rare cases, the presence of this extra chromosome can cause errors in sorting of the chromosomes into the egg or sperm cells, and thus leading to either Prader Willi or Angelman syndromes.

Studies have also been done to specifically examine the role of chromosome 15q duplications in several neurologic and developmental disorders. Moeschler and colleagues (2002) looked for duplications in 400 children with developmental delay and found evidence for duplications in two children (a third child may also have had a duplication but they did not further analyze the chromosomes so it is not clear whether it is really a duplication)2. In contrast, no duplications were found in a study of 285 patients with moderate to severe mental retardation (although they found other abnormalities of chromosome 15) 3. A large study of 3392 patients referred for developmental delay or autism of whom only 540 underwent DNA testing as well as chromosome testing found that ~1/600 cases had an interstitial duplications although they did not mention whether patients with idic(15) chromosomes were also found 4. Two studies that included a total of 226 patients with autism found duplications in ~3% of the patients 5, 6 while only one patient with a duplication was found in a group of 118 patients with epilepsy 7.

What causes them? Why do they occur? When did that happen?

Formation of int dup(15)

We are learning a lot about the structural features of the long arm of chromosome 15 that predisposes it to rearrange and make duplication chromosomes (these same features cause it to delete the same segments of DNA). Chromosomes normally line up during the formation of an egg or sperm and exchange segments of DNA. This alignment occurs early in the formation of the egg and sperm, but because of differences in how these cells develop that is different for an egg or a sperm. In an egg, this alignment while the mother is a fetus in her mother’s uterus. In sperm this occurs continuously from puberty through adult life.

Formation of idic(15)

The alignments have to be done precisely or there will be DNA that is lost or gained during the exchange. To line up correctly, the chromosomes line up based on the sequences of their DNA. On chromosome 15, there are repeated regions that share nearly identical DNA sequence. These sequence repeats lead to duplications and copying errors by predisposing to misalignment of the paired chromosomes. Since errors in lining up contribute to the generation of the duplication chromosome, and this step occurs in the early stages of development of the germ cells (eggs and sperm), it is likely that duplications that arise on the maternal chromosome 15 origninated while the mother was in her mother’s uterus.

There are five main positions that are involved in the generation of duplication chromosomes because of clusters of repetitive DNA sequences along the arm of the chromosome. Importantly, these repeated regions contain active genes, so understanding the positions that are involved in making the duplication chromosomes may help us understand the variability in the symptoms of people who carry duplications- the symptoms may depend on the regions that are duplicated, which repeat was involved and possibly the specific position of the exchange within the repeat.

We know that the part of chromosome 15 is involved in two other disorders, Prader Willi syndrome and Angelman syndrome, how does research on those disorders help us understand duplications of chromosome 15?

Prader Willi and Angelman syndromes are most often caused by deletions of chromosome 15q11-q13. The differences in the symptoms that occur in these disorders are based upon the parental origin of the chromosome that is deleted. Studies in these disorders have focused on determination of which genes in the region are used differently on maternally-derived versus paternally derived chromosomes. This process is called imprinting and is very likely to be important in idic(15) and int dup(15). There are several genes that are active only from the paternal chromosome and two genes that are known to only be active on the maternal chromosome 15. The control region that regulates parent-of-origin specific expression is included in the region that commonly is duplicated in idic(15) and int dup(15). One gene in the region is involved in pigmentation (P gene) and several recent papers have noted unusual skin pigmentation in patients with duplications. In patients with Prader Willi and Angelman syndrome, decreased pigmentation has been noted frequently8. The extra copies of the P gene in dup(15) syndromes, may lead to increased pigmentation in some children9.

Are most duplications are inherited from the mother?

For idic(15) and int dup(15), the symptoms are more obvious if the chromosome came from the mother, because they include the learning disabilities, autistic features, muscle tone changed, and minor facial features. Thus, there is some degree of bias for identifying patients with the maternally derived duplications- they are a lot easier to recognize and more likely to get chromosome testing done. One study in 2004 identified a case of a paternal duplication associated with autism as well 10. Nonetheless, it seems likely that duplications occur more frequently on the maternal chromosome although we are likely to be missing many patients with paternally derived duplication chromosomes. This would be in keeping with what has been reported for the deletions in Prader Willi and Angelman syndromes where the deletions are more common on maternal chromosome and thus lead to Angelman syndrome (estimated at ~1/15,000) and paternal deletions that lead to Prader Willi syndrome are estimated at ~1/30,000.

What do we know about the region that gets duplicated?

The most commonly duplicated region contains at least 20 genes. Of these, two genes are known to be expressed from the maternal copy of chromosome 15 and at least 5 are known to be expressed from the paternal copy of the chromosome. Because maternally derived duplications tend to cause more significant developmental problems, these genes are likely to be important in duplications of chromosome 15. The two genes known (so far) are UBE3A and ATP10A (aka ATP10C). Importantly, the imprinting process that regulates activity of these genes from the specific chromosomes is most apparent in brain, while in other tissues in the body both maternal and paternal genes are active. Note: One of the world’s experts on UBE3A is Dr. Art Beaudet from Baylor College of Medicine, who will be attending the meeting.

The UBE3A gene encodes a protein that is involved in degradation of other proteins in the cell. Loss of protein product arising from errors in the gene or deletion of the gene causes Angelman syndrome. It is expressed by many cells in the body (which actually express both copies of the gene) and nerve cells in the brain, which only use the maternal copy. This gene is present in 4 copies in most children with idic(15) and 3 copies in most patients with interstitial duplications. Studies done by Laura Herzing’s lab have shown that the extra copies of the gene are active in patients with idic(15) chromosomes11.

The ATP10A gene makes a protein that is thought to be involved in moving calcium in and out of cells. It is expressed by the brain and most people with idic(15) chromosomes carry two additional copies of the gene while most children with interstitial duplications have one extra copies.

There are also 3 GABA receptor genes in the region that is commonly duplicated. GABA receptors are neurotransmitter receptors that are inhibitory in function and play important roles in virtually brain functions. A functional GABA receptor is composed of several parts, and it is believed that expressing extra copies of some components will lead to fewer functional receptors although this needs to be tested. In mice, abnormal over- or underexpression of individual parts of GABA receptors often leads to seizures, thus it is likely that the increased numbers of receptors are part of what predisposes kids with duplications of 15q11-q13 to seizures. Many seizure medications target the GABAergc system to try to inhibit seizure activity.

Have there been any studies on treatments for children with chromosome 15 duplications?

A group at the University of California, Davis, reported three families, which included five people with interstitial duplications of chromosome 15. The children had ADHD, PDD or Autism12. 3/5 were treated with methylphenidate (Ritalin) for their ADHD symptoms and responded well. One of these children had also been given a trial of adderall but did not respond as well so was placed back on methylphenidate. Respiridone had mixed effects- for one child it was beneficial and one responded poorly (no details given). Fluoxetine was not beneficial for and of the 3 children treated with it- two had aggressive behaviors and one was reported as not responding. Since the last meeting in 2003, no larger studies have been done to see which medications work best for the behavioral parts of the dup(15) symptoms. Based on the discussions on your list serve and the clinical data that we accumulated as part of our study, we suspect that patients with chromosome 15 duplications may tolerate medications differently and may be more sensitive to side effects for some classes of medications, such at the serotonin reuptake inhibitor type medications (SSRI). Thus, these should be used with caution and any new medication should be instituted in a controlled setting, with slow titration of levels and with a clear endpoint as to what the expected outcome for treatment is. This includes supplements.

What has our study of chromosome 15 duplications found?

Our research study on Molecular Investigations of Duplications of Chromosome 15 in Autism is recruiting new participants in this study through 2008. Most families who enroll after March 1, 2004 will only be asked to participate in the DNA study. See http://www.idic15.org/Schanen.html.

We are looking at various components of the structure of the duplicated chromosomes as well as the symptoms manifest by the child. So far we have gotten samples from 82 people with duplications of chromosome 15 and have done clinical assessments on 60 people. We have also assessed 12 cases that we do not have DNA samples to study.

Nicholas Wang, (now PhD, 2004) performed his doctoral work designing a tool to rapidly assess the size of the duplications and number of copies of the regions that are present. This tool is called array comparative genomic hybridization (array CGH) and involves taking specific pieces of DNA from chromosome 15 and sticking them to a glass slide. The DNA from the person with the duplication is then tagged with a fluorescent green dye and DNA from the parent is then tagged with a fluorescent red dye. The DNAs are then mixed together in equal amounts and allowed to stick to the DNA on the glass slide. They should stick specifically to the ones that they match by sequence. If the number of copies of a specific sequence is the same between the parent and the child, the fluorescence signal from the slide emits yellow light- indicating that both stuck to the slide in about the same amount. If there is a region that is present in higher copy because of the duplication, the green DNA from the patient will be more likely to stick- so there is a bias is the signal toward green.

Parental DNA

Using a laser to capture the amount of green to red signal for each of the spots of DNA on the glass slide and quantitating the relative signal difference, Nick was able to distinguish whether there were 1, 2, 3, or 4 extra copies of the duplication regions. His work allowed us to sort out the differences in the BP4:BP5 versus BP3:BP3 duplications13. (He is now at the Lawrence Berkeley lab in Berkeley California.)

Chromosome findings:

15q11-q14 region

Critical region

Although most reports describe idic(15) chromosomes as mirror images, which would mean that they carry two additional copies of the DNA in the region, we see that most of them are asymmetric and lead to one extra copy of part of the region and two extra copies of other parts of the region. The most common form occurs between an exchange between BP5 and BP4.

Critical region

Critical region

BP5-BP4 exchange

Most common form (BP4-BP5)

Second most common form (BP3:BP3)

Critical region

Critical region


15q11-q14 region

Critical region

Critical region

Of our samples, most are idic(15) but we have several familial cases of int dup(15).

We have not formally analyzed the clinical data but the simple overview of clinical data does not show an obvious correlation of the size of the duplication region with the severity of the symptoms. Detailed analyses are planned when we complete the clinical testing.

Clinical findings:

As noted in the previous meeting, we have been working with the research group at Duke to examine the symptoms of kids with duplications of chromosome 15 compared with typically developing kids and kids that have autism but no chromosome abnormality. Looking at the first 41 kids, we find a remarkable variability in how the kids are doing when we sort them by age. In general, kids with typical interstitial duplications have milder cognitive symptoms and fewer seizures. Children with idic(15) chromosomes tend to sit and walk later than both typically developing and other autistic kids, 95% were walking by age 5 years and the onset of language peaks around age 4-5 years. 14/41 children had their first word by age 5 years, 2 began using words between 5-10 years and one acquired his/her first word after age 10 y. Phrase speech was present in 12/41 children. The average age at first word is 28 months and first phrase 45 months. The children who had better “joint attention” skills (the ability to direct someone else’s attention to something that you are interested in) had better language scores. We also looked at some adaptive skills and 9/41 achieved bladder control by age 78 months (6.5 y, range 30-78m) and 8/41 were toilet trained for bowel and bladder functions by 84 months (7 y, range 30-84 m). We plan to extend these analyses on the larger group when we have completed the clinical assessment.  (+ info)

What is an interstitial deletion of the 7th chromosome?

PLEASE no cut, copy and pasted answers... I need info in regular person talk.. not all the medical humble jumble! Thanks!
I am not sure why you put that about Hypochondria in there... I know what that means.. I am wondering about this because we were told my neice will be born with this defect.. we are trying to learn as much as we can, but all the websites and such are very confusing. My sister does have an appointment with a genetisist (sp?) about this, but that is not for another month.

Yahoo search: interstitial deletion chromosome 7


Untangling thick language from website: It means a child is missing some DNA.


Internal search: interstitial

Situated between the cells of a structure or part.  (+ info)

Can chromosome instability cause an individual to be highly susceptible to cancer?

Yes or no?

There are lots of things that can cause cancer however not many of them has been proven yet. For now I am pretty sure the answer is no but in a few years it might change to a yes  (+ info)

What are four disorders that are associated with chromosome 19 and what are their symptons?

Disco Fever.  (+ info)

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