vania-janet/multiturn-rag-retrieval-data huggingface dataset:
BRCA1
BRCA1 expression is reduced or undetectable in the majority of high grade , ductal breast cancers . It has long been noted that loss of BRCA1 activity , either by germ - line mutations or by down - regulation of gene expression , leads to tumor formation in specific target tissues . In particular , decreased BRCA1 expression contributes to both sporadic and inherited breast tumor progression . Reduced expression of BRCA1 is tumorigenic because it plays an important role in the repair of DNA damages , especially double - strand breaks , by the potentially error - free pathway of homologous recombination . Since cells that lack the BRCA1 protein tend to repair DNA damages by alternative more error - prone mechanisms , the reduction or silencing of this protein generates mutations and gross chromosomal rearrangements that can lead to progression to breast cancer .
BRCA1
Similarly , BRCA1 expression is low in the majority ( 55 % ) of sporadic epithelial ovarian cancers ( EOCs ) where EOCs are the most common type of ovarian cancer , representing approximately 90 % of ovarian cancers . In serous ovarian carcinomas , a sub-category constituting about 2 / 3 of EOCs , low BRCA1 expression occurs in more than 50 % of cases . Bowtell reviewed the literature indicating that deficient homologous recombination repair caused by BRCA1 deficiency is tumorigenic . In particular this deficiency initiates a cascade of molecular events that sculpt the evolution of high - grade serous ovarian cancer and dictate its response to therapy . Especially noted was that BRCA1 deficiency could be the cause of tumorigenesis whether due to BRCA1 mutation or any other event that causes a deficiency of BRCA1 expression .
Cousin marriage
In a different view , William Saletan of Slate magazine accuses the authors of this study of suffering from the `` congenital liberal conceit that science solves all moral questions '' . While readily conceding that banning cousin marriage can not be justified on genetic grounds , Saletan asks rhetorically whether it would be acceptable to legalize uncle - niece marriage or `` hard - core incest '' between siblings and then let genetic screening take care of the resulting problems . A recent New York Times article by Sarah Kershaw documents fear by many married cousins of being treated with derision and contempt . `` While many people have a story about a secret cousin crush or kiss , most Americans find the idea of cousins marrying and having children disturbing or even repulsive , '' notes the article . It gives the example of one mother , Mrs. Spring , whose daughter Kimberly Spring - Winters , 29 , married her cousin Shane Winters , 37 . She stated that when she has told people about her daughter 's marriage , they have been shocked and that consequently she is afraid to mention it . They live in a small Pennsylvania town and she worries that her grandchildren will be treated as outcasts and ridiculed due to their parental status . Another cousin couple stated that their children 's maternal grandparents have never met their two grandchildren because the grandparents severed contact out of disapproval for the couple 's marriage . This couple withheld their names from publication .
Vasopressin
Syndrome of Inappropriate Antidiuretic Hormone secretion ( SIADH ) in turn can be caused by a number of problems . Some forms of cancer can cause SIADH , particularly small cell lung carcinoma but also a number of other tumors . A variety of diseases affecting the brain or the lung ( infections , bleeding ) can be the driver behind SIADH . A number of drugs has been associated with SIADH , such as certain antidepressants ( serotonin reuptake inhibitors and tricyclic antidepressants ) , the anticonvulsant carbamazepine , oxytocin ( used to induce and stimulate labor ) , and the chemotherapy drug vincristine . It has also been associated with fluoroquinolones ( including ciprofloxacin and moxifloxacin ) . Finally , it can occur without a clear explanation . Hyponatremia can be treated pharmaceutically through the use of vasopressin receptor antagonists .
Autophagy
Several experiments have been done with mice and varying Beclin1 , a protein that regulates autophagy . When the Beclin1 gene was altered to be heterozygous ( Beclin 1 + / - ) , the mice were found to be tumor prone . However , when Beclin1 was overexpressed , tumor development was inhibited . Care should be exercised when interpreting phenotypes of beclin mutants and attributing the observations to a defect in autophagy , however : Beclin1 is generally required for phosphatidylinositol 3 - phosphate production and as such it affects numerous lysosomal and endosomal functions , including endocytosis and endocytic degradation of activated growth factor receptors . In support of the possibility that Beclin1 affects cancer development through an autophagy - independent pathway is the fact that core autophagy factors which are not known to affect other cellular processes and are definitely not known to affect cell proliferation and cell death , such as Atg7 or Atg5 , show a much different phenotype when the respective gene is knocked out , which does not include tumor formation . In addition , full knockout of Beclin1 is embryonic lethal whereas knockout of Atg7 or Atg5 is not .
Vietnam War
The US Veterans Administration has listed prostate cancer , respiratory cancers , multiple myeloma , Diabetes mellitus type 2 , B - cell lymphomas , soft - tissue sarcoma , chloracne , porphyria cutanea tarda , peripheral neuropathy , and spina bifida in children of veterans exposed to Agent Orange .
BRCA1
Population or subgroup BRCA1 mutation ( s ) Reference ( s ) African - Americans 943ins10 , M1775R Afrikaners E881X Ashkenazi Jewish 185delAG , 188del11 , 5382insC Austrians 2795delA , C61G , 5382insC , Q1806stop Belgians 2804delAA , IVS5 + 3A > G Dutch Exon 2 deletion , exon 13 deletion , 2804delAA Finns 3745delT , IVS11 - 2A > G French 3600del11 , G1710X French Canadians C4446T Germans 5382insC , 4184del4 Greeks 5382insC Hungarians 300T > G , 5382insC , 185delAG Italians 5083del19 Japanese L63X , Q934X Native North Americans 1510insG , 1506A > G Northern Irish 2800delAA Norwegians 816delGT , 1135insA , 1675delA , 3347delAG Pakistanis 2080insA , 3889delAG , 4184del4 , 4284delAG , IVS14 - 1A > G Polish 300T > G , 5382insC , C61G , 4153delA Russians 5382insC , 4153delA Scottish 2800delAA Spanish R71G Swedish Q563X , 3171ins5 , 1201del11 , 2594delC
BRCA1
Thus , while BRCA1 expression is low in the majority of these cancers , BRCA1 mutation is not a major cause of reduced expression .
BRCA1
ABL1 , AKT1 , AR , ATR , ATM , ATF1 , AURKA , BACH1 , BARD1 , BRCA2 , BRCC3 , BRE , BRIP1 , C - jun , CHEK2 , CLSPN , COBRA1 , CREBBP , CSNK2B , CSTF2 , CDK2 , DHX9 , ELK4 , EP300 , ESR1 , FANCA , FANCD2 , FHL2 , H2AFX , JUNB , JunD , LMO4 , MAP3K3 , MED1 , MED17 , MED21 , MED24 , MRE11A , MSH2 , MSH3 , MSH6 , Myc , NBN , NMI , NPM1 , NCOA2 , NUFIP1 , P53 , PALB2 , POLR2A , PPP1CA , Rad50 , RAD51 , RBBP4 , RBBP7 , RBBP8 , RELA , RB1 , RBL1 , RBL2 , RPL31 , SMARCA4 , SMARCB1 , STAT1 , UBE2D1 , USF2 , VCP , XIST , and ZNF350 .
Telangiectasia
Acne rosacea Blepharitis Environmental damage such as that caused by sun or cold exposure Age Trauma to skin such as contusions or surgical incisions . Radiation exposure such as that experienced during radiotherapy for the treatment of cancer Chemotherapy Carcinoid syndrome Limited systemic sclerosis / scleroderma ( a Scleroderma sub-type ) Chronic treatment with topical corticosteroids may lead to telangiectasia . Spider angiomas are a radial array of tiny arterioles that commonly occur in pregnant women and in patients with hepatic cirrhosis and are associated with palmar erythema . In men , they are related to high estrogen levels secondary to liver disease . Tempi syndrome Smoking
BRCA1
BRCA1 is part of a complex that repairs double - strand breaks in DNA . The strands of the DNA double helix are continuously breaking as they become damaged . Sometimes only one strand is broken , sometimes both strands are broken simultaneously . DNA cross-linking agents are an important source of chromosome / DNA damage . Double - strand breaks occur as intermediates after the crosslinks are removed , and indeed , biallelic mutations in BRCA1 have been identified to be responsible for Fanconi Anemia , Complementation Group S , a genetic disease associated with hypersensitivity to DNA crosslinking agents . BRCA1 is part of a protein complex that repairs DNA when both strands are broken . When this happens , it is difficult for the repair mechanism to `` know '' how to replace the correct DNA sequence , and there are multiple ways to attempt the repair . The double - strand repair mechanism in which BRCA1 participates is homologous recombination , where the repair proteins utilize a template of the identical homologous intact sequence from a sister chromatid , from a homologous chromosome , or from the same chromosome ( depending on cell cycle phase ) . This DNA repair takes place with the DNA in the cell nucleus , wrapped around the histone . Several proteins , including BRCA1 , arrive at the histone - DNA complex for this repair . Regulatory aspect to BRCA1 nuclear ⁄ non-nuclear distribution was first shown by the laboratory of Dr Rao in 1997
Pierre de Coubertin
In 1895 Pierre de Coubertin had married Marie Rothan , the daughter of family friends . Their son Jacques ( 1896 -- 1952 ) became ill after being in the sun too long when he was a little child . Their daughter Renée ( 1902 -- 1968 ) suffered emotional disturbances and never married . Marie and Pierre tried to console themselves with two nephews , but they were killed at the front in World War I. Coubertin died of a heart attack in Geneva , Switzerland on 2 September 1937 . Marie died in 1963 .
BRCA1
BRCA1 and BRCA2 are normally expressed in the cells of breast and other tissue , where they help repair damaged DNA , or destroy cells if DNA can not be repaired . They are involved in the repair of chromosomal damage with an important role in the error - free repair of DNA double - strand breaks . If BRCA1 or BRCA2 itself is damaged by a BRCA mutation , damaged DNA is not repaired properly , and this increases the risk for breast cancer . BRCA1 and BRCA2 have been described as `` breast cancer susceptibility genes '' and `` breast cancer susceptibility proteins '' . The predominate allele has a normal , tumor suppressive function whereas high penetrance mutations in these genes cause a loss of tumor suppressive function which correlates with an increased risk of breast cancer .
Thalidomide
Although the Australian obstetrician William McBride took credit for raising the alarm about Thalidomide it was a midwife who first suspected the drug was causing birth defects in the babies of patients under his care at Crown Street Women 's Hospital in Sydney . German paediatrician Widukind Lenz who also suspected the link is credited with conducting the scientific research that proved Thalidomide was causing birth defects in 1961 . McBride was later awarded a number of honors , including a medal and prize money by L'Institut de la Vie in Paris , but he was eventually struck off the Australian medical register in 1993 for scientific fraud . Further animal tests were conducted by Dr George Somers , Chief Pharmacologist of Distillers Company in Britain , which showed foetal abnormalities in rabbits . Similar results were also published showing these effects in rats and other species .
Cousin marriage
There has been a great deal of debate in the past few years in the United Kingdom about whether to discourage cousin marriages through government public relations campaigns or ban them entirely . The debate has been prompted by a Pakistani immigrant population making up 1.5 % of the British population , of whom about 55 % marry a first cousin . For example , Environment Minister ( later Immigration Minister ) Phil Woolas said in 2008 , `` If you have a child with your cousin the likelihood is there 'll be a genetic problem '' and that such marriages were the `` elephant in the room '' . Physician Mohammad Walji has spoken out against the practice , saying that it is a `` very significant '' cause of infant death , and his practice has produced leaflets warning against it . However , Alan Bittles of the Centre for Comparative Genomics in Australia states that the risk of birth defects rises from roughly 2 % in the general population to 4 % for first cousins and therefore that `` It would be a mistake to ban it '' . Aamra Darr of the University of Leeds has also criticized what she called an `` alarmist presentation of data '' that exaggerates the risk .
Homologous chromosome
A couple of homologous chromosomes , or homologs , are a set of one maternal and one paternal chromosome that pair up with each other inside a cell during meiosis . Homologs have the same genes in the same loci where they provide points along each chromosome which enable a pair of chromosomes to align correctly with each other before separating during meiosis . This is the basis for Mendelian inheritance which characterizes inheritance patterns of genetic material from an organism to its offspring parent developmental cell at the given time and area .
X chromosome
It is estimated that about 10 % of the genes encoded by the X chromosome are associated with a family of `` CT '' genes , so named because they encode for markers found in both tumor cells ( in cancer patients ) as well as in the human testis ( in healthy patients ) .
BRCA1
BRCA1 and BRCA1 ( / ˌbrækəˈwʌn / ) are a human gene and its protein product , respectively . The official symbol ( BRCA1 , italic for the gene , nonitalic for the protein ) and the official name ( breast cancer 1 ) are maintained by the HGNC . Orthologs , styled Brca1 and Brca1 , are common in other mammal species . BRCA1 is a human tumor suppressor gene ( to be specific , a caretaker gene ) , found in all humans ; its protein , also called by the synonym breast cancer type 1 susceptibility protein , is responsible for repairing DNA .
Cell cycle
A disregulation of the cell cycle components may lead to tumor formation . As mentioned above , when some genes like the cell cycle inhibitors , RB , p53 etc . mutate , they may cause the cell to multiply uncontrollably , forming a tumor . Although the duration of cell cycle in tumor cells is equal to or longer than that of normal cell cycle , the proportion of cells that are in active cell division ( versus quiescent cells in G phase ) in tumors is much higher than that in normal tissue . Thus there is a net increase in cell number as the number of cells that die by apoptosis or senescence remains the same .
Eukaryotic transcription
In vertebrates , the majority of gene promoters contain a CpG island with numerous CpG sites . When many of a gene 's promoter CpG sites are methylated the gene becomes silenced . Colorectal cancers typically have 3 to 6 driver mutations and 33 to 66 hitchhiker or passenger mutations . However , transcriptional silencing may be of more importance than mutation in causing progression to cancer . For example , in colorectal cancers about 600 to 800 genes are transcriptionally silenced by CpG island methylation ( see regulation of transcription in cancer ) . Transcriptional repression in cancer can also occur by other epigenetic mechanisms , such as altered expression of microRNAs . In breast cancer , transcriptional repression of BRCA1 may occur more frequently by over-expressed microRNA - 182 than by hypermethylation of the BRCA1 promoter ( see Low expression of BRCA1 in breast and ovarian cancers ) .
BRCA1
Only about 3 % -- 8 % of all women with breast cancer carry a mutation in BRCA1 or BRCA2 . Similarly , BRCA1 mutations are only seen in about 18 % of ovarian cancers ( 13 % germline mutations and 5 % somatic mutations ) .
Cell cycle
Two families of genes , the cip / kip ( CDK interacting protein / Kinase inhibitory protein ) family and the INK4a / ARF ( Inhibitor of Kinase 4 / Alternative Reading Frame ) family , prevent the progression of the cell cycle . Because these genes are instrumental in prevention of tumor formation , they are known as tumor suppressors .
Genetic recombination
Recombination may also occur during mitosis in eukaryotes where it ordinarily involves the two sister chromosomes formed after chromosomal replication . In this case , new combinations of alleles are not produced since the sister chromosomes are usually identical . In meiosis and mitosis , recombination occurs between similar molecules of DNA ( homologs ) . In meiosis , non-sister homologous chromosomes pair with each other so that recombination characteristically occurs between non-sister homologues . In both meiotic and mitotic cells , recombination between homologous chromosomes is a common mechanism used in DNA repair .
Cousin marriage
It 's a form of discrimination that nobody talks about . People worry about not getting health insurance -- but saying that someone should n't marry based on how they 're related , when there 's no known harm , to me is a form of discrimination . ''
Widow's peak
Ely Guv Hintonith and M. Michael Cohen hypothesized the widow 's peak hairline to be an anomaly that results from a lower - than - usual point of intersection of the bilateral periorbital fields of hair - growth suppression on the forehead . This can occur because the periorbital fields of hair - growth suppression are smaller than usual , or because they are more widely spaced . Wide spacing also explains the association between ocular hypertelorism -- that is , the eyes being abnormally far apart -- and widow 's peak ; this was suggested by findings in an unusual case of ocular hypertelorism in which surrounding scalp - hair growth was suppressed by an ectopic ( displaced ) eye . Widow 's peaks are a symptom of Donnai - Barrow syndrome , a rare genetic disorder caused by mutations in the LRP2 gene . Other genetic syndromes occasionally associated with widow 's peaks include Waardenburg syndrome and Aarskog syndrome .
BRCA1
Another microRNA known to reduce expression of BRCA1 in ovarian cancer cells is miR - 9 . Among 58 tumors from patients with stage IIIC or stage IV serous ovarian cancers ( HG - SOG ) , an inverse correlation was found between expressions of miR - 9 and BRCA1 , so that increased miR - 9 may also contribute to reduced expression of BRCA1 in these ovarian cancers .
Genetic recombination
Recombination can occur between DNA sequences that contain no sequence homology . This can cause chromosomal translocations , sometimes leading to cancer .
BRCA1
BRCA1 is also involved in another type of DNA repair , termed mismatch repair . BRCA1 interacts with the DNA mismatch repair protein MSH2 . MSH2 , MSH6 , PARP and some other proteins involved in single - strand repair are reported to be elevated in BRCA1 - deficient mammary tumors .
Genetic recombination
Genetic recombination is the production of offspring with combinations of traits that differ from those found in either parent . In eukaryotes , genetic recombination during meiosis can lead to a novel set of genetic information that can be passed on from the parents to the offspring . Most recombination is naturally occurring .
Asexual reproduction
Polyembryony is a widespread form of asexual reproduction in animals , whereby the fertilized egg or a later stage of embryonic development splits to form genetically identical clones . Within animals , this phenomenon has been best studied in the parasitic Hymenoptera . In the 9 - banded armadillos , this process is obligatory and usually gives rise to genetically identical quadruplets . In other mammals , monozygotic twinning has no apparent genetic basis , though its occurrence is common . There are at least 10 million identical human twins and triplets in the world today .
BRCA1
A patent application for the isolated BRCA1 gene and cancer promoting mutations discussed above , as well as methods to diagnose the likelihood of getting breast cancer , was filed by the University of Utah , National Institute of Environmental Health Sciences ( NIEHS ) and Myriad Genetics in 1994 ; over the next year , Myriad , ( in collaboration with investigators at Endo Recherche , Inc. , HSC Research & Development Limited Partnership , and University of Pennsylvania ) , isolated and sequenced the BRCA2 gene and identified key mutations , and the first BRCA2 patent was filed in the U.S. by Myriad and other institutions in 1995 . Myriad is the exclusive licensee of these patents and has enforced them in the US against clinical diagnostic labs . This business model led from Myriad being a startup in 1994 to being a publicly traded company with 1200 employees and about $500 M in annual revenue in 2012 ; it also led to controversy over high prices and the inability to get second opinions from other diagnostic labs , which in turn led to the landmark Association for Molecular Pathology v. Myriad Genetics lawsuit . The patents began to expire in 2014 .
Homologous chromosome
Homologous chromosomes do not function the same in mitosis as they do in meiosis . Prior to every single mitotic division a cell undergoes , the chromosomes in the parent cell replicate themselves . The homologous chromosomes within the cell will ordinarily not pair up and undergo genetic recombination with each other . Instead , the replicants , or sister chromatids , will line up along the metaphase plate and then separate in the same way as meiosis II - by being pulled apart at their centromeres by nuclear mitotic spindles . If any crossing over does occur between sister chromatids during mitosis , it does not produce any new recombinant genotypes .
Genetic recombination
In eukaryotes , recombination during meiosis is facilitated by chromosomal crossover . The crossover process leads to offspring having different combinations of genes from those of their parents , and can occasionally produce new chimeric alleles . The shuffling of genes brought about by genetic recombination produces increased genetic variation . It also allows sexually reproducing organisms to avoid Muller 's ratchet , in which the genomes of an asexual population accumulate genetic deletions in an irreversible manner .
Polistes carolina
P. carolina , like many eusocial insects , follows a haplodiploidy sex determination system , meaning males are haploid and develop from unfertilized eggs , while females are diploid and develop from fertilized eggs . Daughters share one identical allele from their haploid father and receive the other allele from their diploid mother 's two alleles . This knowledge allows determination of the relatedness among individuals via algorithms and computer programs such as Relatedness 4.2 and Kinship 1.1. 2 . Due to this system of reproduction , genetic relatedness among nestmate foundresses is about 0.75 . Mating males , however , are not related to other males , nor are they related to the females with which they mated .
Cousin marriage
A recent research study of 70 nations has found a statistically significant negative correlation between consanguineous kinship networks and democracy . The authors note that other factors , such as restricted genetic conditions , may also explain this relationship . This follows a 2003 Steve Sailer essay published for The American Conservative , where he claimed that high rates of cousin marriage play an important role in discouraging political democracy . Sailer believes that because families practicing cousin marriage are more related to one another than otherwise , their feelings of family loyalty tend to be unusually intense , fostering nepotism .