623:
genetic elements, are highly susceptible to increases and decreases in number of copies, through duplications or deletions, and the researchers referenced various studies from 2005 to 2009 that found that a higher number of copies contributed to autism severity while a lower number contributed to schizophrenia severity. Since these disorders are fairly common among humans, it was proposed that this explained their prevalence. This model was elaborated on in more detail in a 2018 article that included one of the original authors, in light of new evidence in the intervening years.
294:(~35), single- or low-copy in non-primate mammals and absent in non-mammals. Consequently, the Olduvai domain demonstrates the largest HLS increase in copy number of any protein-coding region over any other living species, an additional ~160 copies compared with chimpanzees. The increase in the number of copies that are present in connection with Olduvai seems to have a direct correlation with several phenotypes of the brain including the increase in brain size as seen through evolution.
440:. There was no significant association found in females. Additionally, it was found that males with higher CON2 numbers appeared to have the largest increases in IQ over other males of the same age at a mean age of 11 years old. The correlation then appeared to decrease with age. A proportional advantage was also present in younger individuals. This corroborated studies that have shown that brain growth in the brightest children, and children with
345:
associated with increasing severity of social impairment in autism. This evidence is relevant for current theories proposing that autism and psychosis are fundamentally related. The precise nature of this relationship is currently under debate, with alternative lines of argument suggesting that the two are diametrically opposed diseases, exist on a continuum or exhibit a more nuanced relationship.
444:, increases after birth and peaks at around age 11 or 12 before slowing down in adulthood. In the second group, birth head circumference was not found to significantly affect IQ, further corroborating these studies. The second cohort had previously had a genetic analysis rule out any effect on IQ of other genome-wide
415:
association with IQ, however, was through its effects on bilateral temporal surface area. Notably, this contribution to IQ was larger than that of its effects on right frontal lobe surface area, despite the fact that it increased this area the most. It was concluded that the
Olduvai domain appears to have a role in
532:, around 450 million years ago, however, the Olduvai domain is not clearly seen until the emergence of mammals. The first Olduvai domain located outside of myomegalin is seen approximately 100–150 million years ago, when the domain was included in a duplication and transposition event which created a new gene,
634:
inverts) that occurred between 1p11.2 and 1q21.2 in the human lineage after the separation from chimpanzees. This was theorised to have contributed to their hyper-amplification specifically in humans, because pairs of chromosomes in which one contains a pericentric inversion and the other does not (a
622:
In 2009, it was proposed that the larger brain size conferred by a high number of
Olduvai domain copies in humans carried an evolutionary advantage which led to the persistence and maintenance of Olduvai copies within this high range. At the same time, the Olduvai domains, like many other repetitive
451:
This association has important implications for understanding the interplay between cognitive function and autism phenotypes. These findings also provide additional support for the involvement of
Olduvai in a genomic trade-off model involving the human brain: the same key genes that have been major
379:
IQ test and the
Progressive Achievement Mathematics test. The strength of the association between CON2 and IQ was reported to be greater than that of any other single genetic candidate reported in any previous study. This effect was significantly more profound in males. The CON2 copy number of most
344:
DUF1220 copy number variation have recently been investigated in autism which is a disorder associated with deletions and duplications of 1q21 yet the causative loci within such regions have not previously been identified. Such research has found that copy number of DUF1220 subtype CON1 is linearly
595:
genes primarily involving a sequential series of three variants of the domain. These three variants were also found in gorilla and chimpanzee genomes but are not repeated in triplet form and are only present in around five copies overall. Based on this, the variants were given the names HLS1, HLS2
366:
investigation of the potential association between DUF1220 and brain size found that DUF1220 copy number decrease is associated with microcephaly in individuals with 1q21 CNVs. Of all 1q21 sequences tested, DUF1220 sequences were the only ones to show consistent correlation between copy number and
414:
increase in IQ, with left temporal surface area being slightly more important. However, it was found that CON2's effects on IQ remained substantial even after eliminating bilateral temporal surface area, right frontal lobe surface area and total grey matter volume as factors. A portion of CON2's
305:
in length and are encoded by a two-exon doublet. Sequences encoding DUF1220 domains show rhythmicity, resonance and signs of positive selection, especially in primates, and are expressed in several human tissues including brain, where their expression is restricted to neurons. The various HLS
374:
and mathematical aptitude scores, a finding replicated in two independent groups from different countries. The study specifically studied the
Olduvai variants CON1 and CON2, noting that measurement of the very high copy number HLS1–3 variants had been challenging given technologies currently
464:
Olduvai domains are one of the many genetic elements located in the 1q21.1 region, which has a high number of repeated elements and therefore a high tendency towards deletions and duplications. This has led to several conditions that involve this region being identified, including
432:
cell divisions, corroborated by higher neuron numbers in primates being associated with
Olduvai copy number. Additionally, studies have shown that cerebral size in primates is almost exclusively correlated with a linear addition of neurons, rather than neuronal size or density.
828:
reported by G. Laureys et al. in 1990. The researchers noticed that a novel protein domain that seemed to match the DUF1220 Pfam entry was present in multiple copies in this gene and in several other places on chromosome 1, which led them to establish 22
651:
and duplications are much more propense to occur. This, combined with the fact that higher copies of
Olduvai domains may have had an evolutionary advantage, could have resulted in the rapid duplication and persistence of Olduvai domains in humans.
353:
Schizophrenia is a neurological condition in which there are issues in brain development. In contrast with autism, copy number increase of DUF1220 subtypes CON1 and HLS1 is associated with reduced severity of positive symptoms in schizophrenia.
419:
proliferation, since this proliferation seems to be the major contributor to lobe surface area while also explaining the effects of
Olduvai dosage that could not be explained by brain region measurements. Corroborating this are stem cell
380:
of the males ranged from 26 to 33, with a mean of 29, and each additional copy was associated with an average IQ score increase of 3.3. CON1 number, on the other hand, was not found to have a significant association with IQ scores.
367:
brain size in both disease (micro/macrocephaly) and non-disease populations. In addition, in primates there is a significant correlation between DUF1220 copy number and both brain size and brain cortical neuron number.
330:
of neurons. When
Olduvai copy number is reduced, neurons appear to mature faster and divide less. Conversely, when Olduvai copy number is increased, neurons appear to mature for longer and divide in higher numbers.
626:
In 2012, a genetic explanation for the high instability and persistence of the
Olduvai-containing regions was put forward: it was found that the HLS Olduvai domains had been affected by a known
391:
surface area showed the strongest association with both CON1 and CON2 copy number. This association was slightly stronger with CON2 copy number. There were no CON1 or CON2 associations with
928:
Popesco MC, Maclaren EJ, Hopkins J, Dumas L, Cox M, Meltesen L, et al. (September 2006). "Human lineage-specific amplification, selection, and neuronal expression of DUF1220 domains".
480:
Studies of deletions and duplications in the 1q21.1 region have consistently revealed microcephaly in association with deletions and macrocephaly in association with duplications.
452:
contributors to the evolutionary expansion of the human brain and human cognitive capacity may also, in different combinations, underlie psychiatric disorders such as autism and
250:
to reach over 20 genes in humans. In humans, Olduvai domains are repeated often dozens of times within these genes. The only other gene an Olduvai domain has been found in is
779:, which shows different colours where the two strands no longer line up. The study found 134 genes that showed human lineage-specific increases in copy number, one of which,
1296:
133:
604:. Hyper-amplification of the triplet resulted in the addition of ~149 copies of Olduvai specifically to the human lineage since its divergence from the genus
406:
These volume and area increases in the grey matter of all cerebral lobes were found to significantly correlate with higher IQ scores. Notably, bilateral
1365:"DUF1220 copy number is associated with schizophrenia risk and severity: implications for understanding autism and schizophrenia as related diseases"
362:
The dosage of the Olduvai protein domain increases along with brain size, which is seen through the evolution from primates to humans. Targeted 1q21
1627:"Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities"
2073:
1475:"DUF1220 copy number is linearly associated with increased cognitive function as measured by total IQ and mathematical aptitude scores"
383:
Brain region associations were also studied. CON1 and CON2 copy number were found to raise the volumes and areas of all four bilateral
209:
and appears to be involved in human brain evolution. The protein domain has also been linked to several neurogenetic disorders such as
77:
741:
376:
768:
591:
It was found in 2012 that the exceptional increase in human Olduvai copy number was a result of multiple duplications within the
707:
that appeared in the human genome did not duplicate as a single gene, but rather did so as a two-gene module, composed of one
153:
644:
370:
A 2015 study found that Olduvai copy number is linearly correlated with increased cognitive function, as measured by total
776:
1094:"Solution NMR backbone assignment reveals interaction-free tumbling of human lineage-specific Olduvai protein domains"
810:(neuroblastoma breakpoint family) gene family, which contains all the known Olduvai domains except the one found in
437:
424:
that have also shown Olduvai's proliferative effects neuronal stem cells. However, Olduvai also had effects on
759:
The Olduvai domain was first identified in 2004 in a study of copy number differences between human and great
141:
301:
in region 1q21.1-q21.2, with several copies also found at 1p36, 1p13.3, and 1p12. They are approximately 65
793:
IMAGE:843276), contained six Olduvai domains. The domain remained unnamed as of that time and was given a
798:
474:
1194:"DUF1220 dosage is linearly associated with increasing severity of the three primary symptoms of autism"
82:
1963:"A novel gene family NBPF: intricate structure generated by gene duplications during primate evolution"
1245:"Replicated linear association between DUF1220 copy number and severity of social impairment in autism"
772:
307:
194:
173:
169:
165:
137:
821:
2114:
2077:
1625:
Brunetti-Pierri N, Berg JS, Scaglia F, Belmont J, Bacino CA, Sahoo T, et al. (December 2008).
1415:
Dumas LJ, O'Bleness MS, Davis JM, Dickens CM, Anderson N, Keeney JG, et al. (September 2012).
814:, was independently identified by Vandepoele et al. in 2005 as a result of a gene (which was named
470:
1861:"Paired involvement of human-specific Olduvai domains and NOTCH2NL genes in human brain evolution"
1338:
17:
1473:
Davis JM, Searles VB, Anderson N, Keeney J, Raznahan A, Horwood LJ, et al. (January 2015).
992:
O'Bleness MS, Dickens CM, Dumas LJ, Kehrer-Sawatzki H, Wyckoff GJ, Sikela JM (September 2012).
445:
375:
available. It found that those with a higher number of copies of CON2 had higher scores on the
1810:
Dumas L, Kim YH, Karimpour-Fard A, Cox M, Hopkins J, Pollack JR, Sikela JM (September 2007).
640:
627:
2109:
1143:"The case for DUF1220 domain dosage as a primary contributor to anthropoid brain expansion"
1043:"High resolution measurement of DUF1220 domain copy number from whole genome sequence data"
937:
120:
1092:
Issaian A, Schmitt L, Born A, Nichols PJ, Sikela J, Hansen K, et al. (October 2019).
727:
genes underwent human-specific hyper-amplification, increasing from 13 copies (encoded by
703:
partner. This striking genomic arrangement suggests that each of the additional copies of
8:
648:
1674:
Mefford HC, Sharp AJ, Baker C, Itsara A, Jiang Z, Buysse K, et al. (October 2008).
941:
2060:
2020:
1887:
1860:
1836:
1811:
1752:
1727:
1700:
1675:
1651:
1626:
1602:
1577:
1550:
1523:
1499:
1474:
1441:
1416:
1389:
1364:
1269:
1244:
1220:
1193:
1169:
1142:
1118:
1093:
1069:
1042:
1018:
993:
961:
900:
873:
488:
Genome sequences indicate that the Olduvai protein domain first appears as part of the
384:
1938:
1911:
1910:
Fortna A, Kim Y, MacLaren E, Marshall K, Hahn G, Meltesen L, et al. (July 2004).
1578:"Genomic trade-offs: are autism and schizophrenia the steep price of the human brain?"
686:, none are functional. Immediately adjacent to, and downstream of, each of these four
2052:
2032:
1984:
1943:
1892:
1841:
1812:"Gene copy number variation spanning 60 million years of human and primate evolution"
1792:
1757:
1705:
1656:
1607:
1555:
1504:
1446:
1394:
1319:
1274:
1225:
1174:
1123:
1074:
1023:
953:
905:
323:
291:
235:
160:
128:
2064:
2024:
58:
2044:
2012:
1974:
1933:
1923:
1882:
1872:
1831:
1823:
1784:
1747:
1739:
1695:
1687:
1646:
1638:
1597:
1589:
1545:
1535:
1494:
1486:
1436:
1428:
1417:"DUF1220-domain copy number implicated in human brain-size pathology and evolution"
1384:
1376:
1311:
1264:
1256:
1215:
1205:
1164:
1154:
1113:
1105:
1064:
1054:
1013:
1005:
965:
945:
895:
890:
885:
553:
549:
516:
especially, that lacks Olduvai sequences but, when mutated, has been implicated in
416:
247:
116:
2048:
2095:
1928:
1676:"Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes"
1210:
425:
70:
723:
partners) went from one gene to four in humans, DUF1220 copies encoded by these
496:) on chromosome 1q36 in mammals at least 200 million years ago. Myomegalin is a
1877:
1432:
1292:
1109:
688:
636:
202:
2007:
Check E (August 2006). "Multiple copies of a mystery gene may make us human".
1788:
1775:
Bond J, Woods CG (February 2006). "Cytoskeletal genes regulating brain size".
1593:
1490:
1315:
1260:
1059:
2103:
1912:"Lineage-specific gene duplication and loss in human and great ape evolution"
1540:
1192:
Davis JM, Searles VB, Anderson N, Keeney J, Dumas L, Sikela JM (March 2014).
1159:
841:
825:
453:
448:
they had, further suggesting a critical period of activity of CON1 and CON2.
407:
267:, and all of these genes have been implicated in the development of neurons.
218:
210:
1979:
1962:
1743:
949:
318:
Research has found that the Olduvai domain has a role in the development of
2056:
1988:
1947:
1896:
1845:
1796:
1761:
1709:
1660:
1611:
1559:
1508:
1450:
1398:
1323:
1278:
1229:
1178:
1127:
1078:
1027:
957:
909:
845:
581:
561:
517:
466:
421:
396:
392:
388:
327:
298:
222:
1691:
1009:
2016:
1961:
Vandepoele K, Van Roy N, Staes K, Speleman F, van Roy F (November 2005).
994:"Evolutionary history and genome organization of DUF1220 protein domains"
848:, to reflect data indicating its role in human brain size and evolution.
606:
565:
505:
400:
302:
225:, to reflect data indicating its role in human brain size and evolution.
206:
1380:
991:
1827:
811:
631:
525:
509:
489:
279:
254:
399:
index. CON1 and CON2 number had been previously found to correlate to
217:(in increased copies). In 2018, it was named by its discoverers after
585:
557:
529:
521:
363:
287:
275:
261:
genes via duplication. Myomegalin itself arose from a duplication of
251:
94:
874:"Changing the name of the NBPF/DUF1220 domain to the Olduvai domain"
174:
http://www.bmrb.wisc.edu/data_library/summary/index.php?bmrbId=27775
170:
http://www.bmrb.wisc.edu/data_library/summary/index.php?bmrbId=27533
166:
http://www.bmrb.wisc.edu/data_library/summary/index.php?bmrbId=27569
2091:
1642:
1339:"Improving lives affected by schizophrenia-related brain disorders"
1297:"Psychosis and autism as diametrical disorders of the social brain"
692:
662:
538:, which would eventually later give rise to a family of duplicated
501:
263:
65:
655:
1624:
1363:
Searles Quick VB, Davis JM, Olincy A, Sikela JM (December 2015).
786:
573:
497:
322:. Specifically, it appears to function to increase the number of
283:
243:
239:
89:
844:
in Tanzania, one of the most important archaeological sites for
297:
In the human genome, DUF1220 sequences are located primarily on
221:
in Tanzania, one of the most important archaeological sites for
1728:"DUF1220 domains, cognitive disease, and human brain evolution"
781:
764:
747:
735:
729:
682:
located on 1p11.2. While chimpanzee and gorilla have copies of
611:
569:
513:
441:
429:
319:
214:
205:
that shows a striking human lineage-specific (HLS) increase in
148:
1960:
1414:
1362:
824:
at 1q36 (i.e. it was located at the breakpoint) in a boy with
2035:(September 2006). "Mining the molecules that made our mind".
816:
699:
gene with its DUF1220 domains in the same orientation as its
534:
274:(~289, with person-to-person variations), reduced in African
271:
459:
2087:
927:
806:
794:
790:
771:(CGH), which takes single DNA strands from each source and
696:
540:
230:
110:
53:
1472:
1191:
357:
1909:
1809:
1091:
820:) being found to have existed at and been disrupted by a
760:
577:
1242:
1041:
Astling DP, Heft IE, Jones KL, Sikela JM (August 2017).
1859:
Fiddes IT, Pollen AA, Davis JM, Sikela JM (July 2019).
1858:
1673:
371:
2086:
This article incorporates text from the public domain
1040:
840:
In 2018, DUF1220 was renamed by its discoverers after
775:
them, or joins them such that they line up, and uses
733:) to 132 (i.e., adding 119 DUF1220 copies encoded by
306:
domains do not show any interactions as suggested by
987:
985:
983:
981:
979:
977:
975:
617:
1732:
Cold Spring Harbor Symposia on Quantitative Biology
1575:
1410:
1408:
1243:Davis JM, Searles Quick VB, Sikela JM (June 2015).
428:thickness that appeared to be the result of mature
1852:
27:Protein domain implicated in human brain evolution
1140:
972:
2101:
1405:
2071:
1721:
1719:
1571:
1569:
1468:
1466:
1464:
1462:
1460:
656:Relation to NOTCH2NL genes in brain development
1141:Keeney JG, Dumas L, Sikela JM (24 June 2014).
923:
921:
919:
867:
865:
863:
861:
213:(in reduced copies) and increased severity of
1291:
871:
1954:
1903:
1803:
1768:
1716:
1667:
1618:
1576:Sikela JM, Searles Quick VB (January 2018).
1566:
1457:
1356:
436:It was found that CON2's effects on IQ were
1725:
1524:"Autism As a Disorder of High Intelligence"
1336:
916:
858:
630:(in which the region around a chromosome's
410:surface area appeared to correlate with a
2072:Lemonick MD, Dorfman A (1 October 2006).
1978:
1937:
1927:
1886:
1876:
1835:
1774:
1751:
1699:
1650:
1601:
1549:
1539:
1498:
1440:
1388:
1268:
1219:
1209:
1168:
1158:
1117:
1068:
1058:
1017:
899:
889:
460:1q21.1 deletion and duplication syndromes
469:and the more general classifications of
334:
2031:
769:array comparative genomic hybridization
358:Cognitive brain function and brain size
14:
2102:
1521:
270:Olduvai copy number is the highest in
2006:
833:genes, and they named the domain the
614:) approximately 6 million years ago.
238:and experienced a rapid expansion in
1344:. Letter to Dr. Elinore McCance-Katz
645:non-allelic homologous recombination
1680:The New England Journal of Medicine
600:, and together they were named the
328:prolonging the developmental period
257:, believed to be the origin of the
24:
1999:
1421:American Journal of Human Genetics
572:). It was also found that several
310:backbone chemical shift analyses.
25:
2126:
1337:Stalters L, Cho R (21 May 2018).
1310:(3): 241–61, discussion 261–320.
1304:The Behavioral and Brain Sciences
618:Evolutionary adaptation in humans
228:Olduvai domains form the core of
801:when entered into its database.
348:
1967:Molecular Biology and Evolution
1777:Current Opinion in Cell Biology
1515:
1330:
1147:Frontiers in Human Neuroscience
234:genes, which first appeared in
1285:
1236:
1185:
1134:
1085:
1034:
891:10.12688/f1000research.13586.1
660:There are four human-specific
13:
1:
2049:10.1126/science.313.5795.1908
872:Sikela JM, van Roy F (2018).
851:
524:of myomegalin can be seen in
387:studied. Most notably, right
105:Available protein structures:
1929:10.1371/journal.pbio.0020207
1522:Crespi BJ (1 January 2016).
1211:10.1371/journal.pgen.1004241
1098:Biomolecular NMR Assignments
483:
7:
1726:Dumas L, Sikela JM (2009).
799:domains of unknown function
475:1q21.1 duplication syndrome
313:
10:
2131:
2085:
2074:"What Makes us Different?"
1878:10.1007/s00439-019-02018-4
1433:10.1016/j.ajhg.2012.07.016
1110:10.1007/s12104-019-09902-0
754:
308:nuclear magnetic resonance
195:domain of unknown function
1789:10.1016/j.ceb.2005.11.004
1594:10.1007/s00439-017-1865-9
1528:Frontiers in Neuroscience
1491:10.1007/s00439-014-1489-2
1316:10.1017/S0140525X08004214
1295:, Badcock C (June 2008).
1261:10.1007/s00439-015-1537-6
1060:10.1186/s12864-017-3976-z
822:chromosomal translocation
678:, located on 1q21.1, and
500:(duplicated relative) of
438:strongly dependent on sex
403:volume in another study.
339:
159:
147:
127:
109:
104:
100:
88:
76:
64:
52:
44:
39:
34:
1541:10.3389/fnins.2016.00300
1369:Translational Psychiatry
1160:10.3389/fnhum.2014.00427
508:protein involved in the
471:1q21.1 deletion syndrome
1744:10.1101/sqb.2009.74.025
950:10.1126/science.1127980
639:) have difficulties in
548:gene has been found in
2076:. Time. Archived from
598:human lineage-specific
446:copy number variations
290:), further reduced in
189:, known until 2018 as
1980:10.1093/molbev/msi222
1692:10.1056/NEJMoa0805384
1010:10.1534/g3.112.003061
797:placeholder name for
628:pericentric inversion
588:) had lost the gene.
335:Clinical significance
2017:10.1038/news060828-5
719:paralogs (and their
544:genes. At least one
1381:10.1038/tp.2015.192
942:2006Sci...313.1304P
602:HLS DUF1220 triplet
2080:on 4 October 2006.
1828:10.1101/gr.6557307
777:fluorescent dyeing
643:which can lead to
385:lobes of the brain
2043:(5795): 1908–11.
610:(chimpanzees and
324:neural stem cells
292:Old World monkeys
236:placental mammals
183:
182:
179:
178:
154:structure summary
16:(Redirected from
2122:
2081:
2068:
2028:
1993:
1992:
1982:
1958:
1952:
1951:
1941:
1931:
1907:
1901:
1900:
1890:
1880:
1856:
1850:
1849:
1839:
1807:
1801:
1800:
1772:
1766:
1765:
1755:
1723:
1714:
1713:
1703:
1671:
1665:
1664:
1654:
1622:
1616:
1615:
1605:
1573:
1564:
1563:
1553:
1543:
1519:
1513:
1512:
1502:
1470:
1455:
1454:
1444:
1412:
1403:
1402:
1392:
1360:
1354:
1353:
1351:
1349:
1343:
1334:
1328:
1327:
1301:
1289:
1283:
1282:
1272:
1240:
1234:
1233:
1223:
1213:
1189:
1183:
1182:
1172:
1162:
1138:
1132:
1131:
1121:
1089:
1083:
1082:
1072:
1062:
1038:
1032:
1031:
1021:
989:
970:
969:
936:(5791): 1304–7.
925:
914:
913:
903:
893:
869:
715:gene. While the
554:Euarchontoglires
550:Laurasiatherians
417:neural stem cell
278:(~125 copies in
102:
101:
32:
31:
21:
2130:
2129:
2125:
2124:
2123:
2121:
2120:
2119:
2115:Protein domains
2100:
2099:
2098:
2084:
2002:
2000:Further reading
1997:
1996:
1973:(11): 2265–74.
1959:
1955:
1908:
1904:
1857:
1853:
1816:Genome Research
1808:
1804:
1773:
1769:
1724:
1717:
1686:(16): 1685–99.
1672:
1668:
1637:(12): 1466–71.
1631:Nature Genetics
1623:
1619:
1574:
1567:
1520:
1516:
1471:
1458:
1413:
1406:
1361:
1357:
1347:
1345:
1341:
1335:
1331:
1299:
1290:
1286:
1241:
1237:
1204:(3): e1004241.
1190:
1186:
1139:
1135:
1090:
1086:
1039:
1035:
990:
973:
926:
917:
870:
859:
854:
785:(then known as
757:
658:
620:
560:(but not other
528:as far back as
486:
462:
360:
351:
342:
337:
316:
28:
23:
22:
15:
12:
11:
5:
2128:
2118:
2117:
2112:
2083:
2082:
2069:
2029:
2003:
2001:
1998:
1995:
1994:
1953:
1902:
1871:(7): 715–721.
1865:Human Genetics
1851:
1822:(9): 1266–77.
1802:
1767:
1715:
1666:
1643:10.1038/ng.279
1617:
1582:Human Genetics
1565:
1514:
1479:Human Genetics
1456:
1404:
1355:
1329:
1284:
1249:Human Genetics
1235:
1184:
1133:
1104:(2): 339–343.
1084:
1033:
971:
915:
884:(2185): 2185.
856:
855:
853:
850:
763:species using
756:
753:
657:
654:
637:heterozygosity
619:
616:
596:and HLS3, for
564:), but not in
485:
482:
461:
458:
359:
356:
350:
347:
341:
338:
336:
333:
315:
312:
203:protein domain
197:1220) and the
187:Olduvai domain
181:
180:
177:
176:
163:
157:
156:
151:
145:
144:
131:
125:
124:
114:
107:
106:
98:
97:
92:
86:
85:
80:
74:
73:
68:
62:
61:
56:
50:
49:
46:
42:
41:
37:
36:
35:Olduvai domain
26:
9:
6:
4:
3:
2:
2127:
2116:
2113:
2111:
2108:
2107:
2105:
2097:
2093:
2089:
2079:
2075:
2070:
2066:
2062:
2058:
2054:
2050:
2046:
2042:
2038:
2034:
2030:
2026:
2022:
2018:
2014:
2010:
2005:
2004:
1990:
1986:
1981:
1976:
1972:
1968:
1964:
1957:
1949:
1945:
1940:
1935:
1930:
1925:
1921:
1917:
1913:
1906:
1898:
1894:
1889:
1884:
1879:
1874:
1870:
1866:
1862:
1855:
1847:
1843:
1838:
1833:
1829:
1825:
1821:
1817:
1813:
1806:
1798:
1794:
1790:
1786:
1783:(1): 95–101.
1782:
1778:
1771:
1763:
1759:
1754:
1749:
1745:
1741:
1737:
1733:
1729:
1722:
1720:
1711:
1707:
1702:
1697:
1693:
1689:
1685:
1681:
1677:
1670:
1662:
1658:
1653:
1648:
1644:
1640:
1636:
1632:
1628:
1621:
1613:
1609:
1604:
1599:
1595:
1591:
1587:
1583:
1579:
1572:
1570:
1561:
1557:
1552:
1547:
1542:
1537:
1533:
1529:
1525:
1518:
1510:
1506:
1501:
1496:
1492:
1488:
1484:
1480:
1476:
1469:
1467:
1465:
1463:
1461:
1452:
1448:
1443:
1438:
1434:
1430:
1427:(3): 444–54.
1426:
1422:
1418:
1411:
1409:
1400:
1396:
1391:
1386:
1382:
1378:
1374:
1370:
1366:
1359:
1340:
1333:
1325:
1321:
1317:
1313:
1309:
1305:
1298:
1294:
1288:
1280:
1276:
1271:
1266:
1262:
1258:
1255:(6): 569–75.
1254:
1250:
1246:
1239:
1231:
1227:
1222:
1217:
1212:
1207:
1203:
1199:
1198:PLOS Genetics
1195:
1188:
1180:
1176:
1171:
1166:
1161:
1156:
1152:
1148:
1144:
1137:
1129:
1125:
1120:
1115:
1111:
1107:
1103:
1099:
1095:
1088:
1080:
1076:
1071:
1066:
1061:
1056:
1052:
1048:
1044:
1037:
1029:
1025:
1020:
1015:
1011:
1007:
1004:(9): 977–86.
1003:
999:
995:
988:
986:
984:
982:
980:
978:
976:
967:
963:
959:
955:
951:
947:
943:
939:
935:
931:
924:
922:
920:
911:
907:
902:
897:
892:
887:
883:
879:
878:F1000Research
875:
868:
866:
864:
862:
857:
849:
847:
843:
842:Olduvai Gorge
838:
836:
832:
827:
826:neuroblastoma
823:
819:
818:
813:
809:
808:
802:
800:
796:
792:
788:
784:
783:
778:
774:
770:
766:
762:
752:
750:
749:
744:
743:
738:
737:
732:
731:
726:
722:
718:
714:
711:gene and one
710:
706:
702:
698:
694:
691:
690:
685:
681:
677:
673:
669:
665:
664:
653:
650:
646:
642:
641:recombination
638:
633:
629:
624:
615:
613:
609:
608:
603:
599:
594:
589:
587:
583:
579:
575:
571:
567:
563:
559:
555:
551:
547:
543:
542:
537:
536:
531:
527:
523:
519:
515:
511:
507:
503:
499:
495:
491:
481:
478:
476:
472:
468:
457:
455:
454:schizophrenia
449:
447:
443:
439:
434:
431:
427:
423:
418:
413:
409:
404:
402:
398:
394:
390:
386:
381:
378:
373:
368:
365:
355:
349:Schizophrenia
346:
332:
329:
325:
321:
311:
309:
304:
300:
295:
293:
289:
285:
281:
277:
273:
268:
266:
265:
260:
256:
253:
249:
245:
241:
237:
233:
232:
226:
224:
220:
219:Olduvai Gorge
216:
212:
211:schizophrenia
208:
204:
200:
196:
192:
188:
175:
171:
167:
164:
162:
158:
155:
152:
150:
146:
143:
139:
135:
132:
130:
126:
122:
118:
115:
112:
108:
103:
99:
96:
93:
91:
87:
84:
81:
79:
75:
72:
69:
67:
63:
60:
57:
55:
51:
47:
43:
38:
33:
30:
19:
2078:the original
2040:
2036:
2008:
1970:
1966:
1956:
1919:
1916:PLOS Biology
1915:
1905:
1868:
1864:
1854:
1819:
1815:
1805:
1780:
1776:
1770:
1735:
1731:
1683:
1679:
1669:
1634:
1630:
1620:
1585:
1581:
1531:
1527:
1517:
1485:(1): 67–75.
1482:
1478:
1424:
1420:
1375:(12): e697.
1372:
1368:
1358:
1346:. Retrieved
1332:
1307:
1303:
1287:
1252:
1248:
1238:
1201:
1197:
1187:
1150:
1146:
1136:
1101:
1097:
1087:
1050:
1047:BMC Genomics
1046:
1036:
1001:
997:
933:
929:
881:
877:
846:early humans
839:
834:
830:
815:
805:
803:
780:
758:
746:
740:
734:
728:
724:
720:
716:
712:
708:
704:
700:
687:
683:
679:
675:
671:
667:
661:
659:
625:
621:
605:
601:
597:
592:
590:
584:(containing
582:eulipotyphla
568:(containing
562:Afrotherians
545:
539:
533:
518:microcephaly
493:
487:
479:
467:TAR syndrome
463:
450:
435:
411:
405:
397:gyrification
393:white matter
389:frontal lobe
382:
369:
361:
352:
343:
317:
299:chromosome 1
296:
269:
262:
258:
229:
227:
223:early humans
198:
190:
186:
184:
29:
2110:Human genes
2009:Nature News
1922:(7): E207.
1588:(1): 1–13.
835:NBPF repeat
647:, in which
566:Xenarthrans
526:vertebrates
506:centrosomal
412:progressive
401:grey matter
303:amino acids
280:chimpanzees
248:duplication
207:copy number
199:NBPF repeat
40:Identifiers
2104:Categories
1738:: 375–82.
1348:20 October
1053:(1): 614.
852:References
812:myomegalin
773:hybridizes
632:centromere
510:cell cycle
490:myomegalin
395:volume or
288:orangutans
276:great apes
255:myomegalin
246:) through
117:structures
2096:IPR010630
2033:Pennisi E
680:NOTCH2NLR
676:NOTCH2NLC
672:NOTCH2NLB
668:NOTCH2NLA
649:deletions
586:hedgehogs
558:elephants
530:bony fish
522:Orthologs
484:Evolution
364:array CGH
286:, ~92 in
282:, ~99 in
252:mammalian
71:IPR010630
2092:InterPro
2065:44285466
2057:17008520
2025:85292818
1989:16079250
1948:15252450
1897:31087184
1846:17666543
1797:16337370
1762:19850849
1710:18784092
1661:19029900
1612:29335774
1560:27445671
1509:25287832
1451:22901949
1399:26670282
1324:18578904
1293:Crespi B
1279:25758905
1230:24651471
1179:25009482
1128:31264103
1079:28807002
1028:22973535
958:16946073
910:29399325
717:NOTCH2NL
709:NOTCH2NL
705:NOTCH2NL
701:NOTCH2NL
693:paralogs
684:NOTCH2NL
663:NOTCH2NL
635:form of
502:CDK5RAP2
426:cortical
422:cultures
408:temporal
314:Function
284:gorillas
264:CDK5RAP2
134:RCSB PDB
66:InterPro
2037:Science
1888:6611739
1837:1950895
1753:2902282
1701:2703742
1652:2680128
1603:5898792
1551:4927579
1534:: 300.
1500:5898241
1442:3511999
1390:5068589
1270:5886748
1221:3961203
1170:4067907
1153:: 427.
1119:6715528
1070:5556342
1019:3429928
966:6878260
938:Bibcode
930:Science
901:5773923
787:MGC8902
755:History
666:genes:
612:bonobos
574:rodents
514:neurons
498:paralog
494:PDE4DIP
320:neurons
244:simians
240:monkeys
201:, is a
191:DUF1220
95:PS51316
90:PROSITE
83:SM01148
59:PF06758
48:Olduvai
18:DUF1220
2063:
2055:
2023:
1987:
1946:
1939:449870
1936:
1895:
1885:
1844:
1834:
1795:
1760:
1750:
1708:
1698:
1659:
1649:
1610:
1600:
1558:
1548:
1507:
1497:
1449:
1439:
1397:
1387:
1322:
1277:
1267:
1228:
1218:
1177:
1167:
1126:
1116:
1077:
1067:
1026:
1016:
964:
956:
908:
898:
782:NBPF15
767:-wide
765:genome
748:NBPF19
742:NBPF14
736:NBPF10
730:NBPF26
695:is an
570:sloths
492:gene (
442:autism
430:neuron
340:Autism
272:humans
215:autism
149:PDBsum
123:
113:
45:Symbol
2061:S2CID
2021:S2CID
1342:(PDF)
1300:(PDF)
962:S2CID
817:NBPF1
689:NOTCH
535:NBPF1
512:, of
78:SMART
2090:and
2088:Pfam
2053:PMID
1985:PMID
1944:PMID
1893:PMID
1842:PMID
1793:PMID
1758:PMID
1706:PMID
1657:PMID
1608:PMID
1556:PMID
1505:PMID
1447:PMID
1395:PMID
1350:2018
1320:PMID
1275:PMID
1226:PMID
1175:PMID
1124:PMID
1075:PMID
1024:PMID
954:PMID
906:PMID
831:NBPF
807:NBPF
804:The
795:Pfam
791:cDNA
745:and
725:NBPF
721:NBPF
713:NBPF
697:NBPF
674:and
593:NBPF
580:and
578:bats
556:and
546:NBPF
541:NBPF
504:, a
473:and
377:WISC
259:NBPF
231:NBPF
185:The
142:PDBj
138:PDBe
121:ECOD
111:Pfam
54:Pfam
2045:doi
2041:313
2013:doi
1975:doi
1934:PMC
1924:doi
1883:PMC
1873:doi
1869:138
1832:PMC
1824:doi
1785:doi
1748:PMC
1740:doi
1696:PMC
1688:doi
1684:359
1647:PMC
1639:doi
1598:PMC
1590:doi
1586:137
1546:PMC
1536:doi
1495:PMC
1487:doi
1483:134
1437:PMC
1429:doi
1385:PMC
1377:doi
1312:doi
1265:PMC
1257:doi
1253:134
1216:PMC
1206:doi
1165:PMC
1155:doi
1114:PMC
1106:doi
1065:PMC
1055:doi
1014:PMC
1006:doi
946:doi
934:313
896:PMC
886:doi
761:ape
751:).
607:Pan
326:by
161:PDB
129:PDB
2106::
2094::
2059:.
2051:.
2039:.
2019:.
2011:.
1983:.
1971:22
1969:.
1965:.
1942:.
1932:.
1918:.
1914:.
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960:.
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880:.
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860:^
837:.
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372:IQ
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136:;
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2067:.
2047::
2027:.
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1920:2
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