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Table 1 Selected examples of human-specific regulatory elements tested in functional assays that showed gain or loss of function

From: Human evolution: the non-coding revolution

HAR

Genome Location (hg19)

Closest gene

Experimental approach

Biological function

Domain of expression

Reported functional difference

Postulated phenotypic association

Reference

HAR1

chr20:61,733,447–61,733,630

HAR1F; HAR1R

qPCR; in situ hybridization

RNA gene

Cajal-Retzius neurons

RNA secondary structure

Brain development

[18]

HAR2/HACNS1

chr2:236773664–236774209

AGAP1 (CENTG2); GBX2

Transgenic mice

Enhancer

Limb, branchial arches

Gain of function

Limb development

[59]

2xHAR.142

chr14:34048651–34048815

NPAS3

Transgenic mice

Enhancer

Forebrain, midbrain, spinal cord

Gain of function

Brain development

[57]

HAR202

chr14:34045570–34045772

NPAS3

Transgenic zebrafish

Enhancer

Central nervous system

Loss of function

Brain development

[58]

ANC516

chr10:36238421–36239039

FZD8

Transgenic mice

Enhancer

Forebrain, midbrain, spinal cord

Gain of function

Brain development

[56]

2xHAR.238

chr2:121832784–121833140

GLI2, TFCP2L1

Transgenic mice

Enhancer

Forebrain, midbrain, hindbrain and spinal cord

Loss of function

Brain development

[37]

2xHAR.114

chr20:30425200–30425393

MYLK2, FOXS1

Transgenic mice

Enhancer

Limb and spinal cord

Loss of function

Limb development

[37]

2xHAR.164

chr2:133346894–133347089

ANKRD30BL, GPR39, LYPD1, NCKAP5

Transgenic mice

Enhancer

Forebrain, midbrain, hindbrain, spinal cord

Gain of function

Brain development

[37]

2xHAR.170

chr5:153640309–153640363

GALNT10, SAP30L, HAND1

Transgenic mice

Enhancer

Isthmus and spinal cord

Loss and gain of function

Brain development

[37]

HAR25

chr4:182271922–182272882

ODZ3

Transgenic mice

Enhancer

Eye

Loss of function

Eye development

[37]

ANC705

chr15:61,979,891–61,980,090

VPS13C, RORA

Epigenetic marks

Enhancer

Neural crest

Gain of function

Neural crest development

[44]

HAR89; 2xHAR.305

chr1:3,089,780–3,089,980

PRDM16

Epigenetic marks

Enhancer

Neural crest

Gain of function (chimp)

Neural crest development

[44]

2xHAR.236

chr1:53,992,480–53,992,679

GLIS1

Epigenetic marks

ENHANCER

Neural crest

Gain of function (chimp)

Neural crest development

[44]

HACNS825

chr2:217,728,749–217,728,948

TNP1; LOC105373876

Epigenetic marks

ENHANCER

Neural crest

Gain of function (chimp)

Neural crest development

[44]

2xHAR87

chr11:115648183–115648526

CADM1

Epigenetic marks and 4-C

ENHANCER

Cerebellum

Gain of function compared to macaque

Synapse regulation

[43]

DAR-12/HACNS219

chr5:158227696–158229500

RNF145

Luciferase

ENHANCER

SK-N-MC cells

Gain of function

Hematological traits

[38]