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Although recent success in reverse genetics has facilitated rapid progress in basic and applied research, integration of forward genetics with modern technologies remains challenging in this important species, as up to 47% of its chromosome is refractory to genetic mapping due to extremely low rate of recombination. Here, we report the development of a marker-assisted mapping strategy to readily screen for and genotype only the rare but informative recombinants, drastically increasing both the resolution and signal-to-noise ratio. Using marker-assisted mapping, we mapped a transgene that was inserted in a &amp;gt;100-Mb recombination desert and a sex-linked spontaneous red-eye (re) mutation just outside the region. We subsequently determined, by CRISPR\/Cas9-mediated knockout, that cardinal is the causal gene of re, which is the first forward genetic identification of a causal gene in Ae. aegypti. The identification of the causal gene of the sex-linked re mutation provides the molecular foundation for using gene editing to develop versatile and stable genetic sexing methods. To facilitate genome-wide forward genetics in Ae. aegypti, we generated and compiled a number of lines with markers throughout the genome. Thus, by overcoming the challenges presented by the vast recombination deserts and the scarcity of markers, we have shown that effective forward genetic analysis is increasingly feasible in this important arboviral vector species.<\/jats:p>","DOI":"10.1093\/genetics\/iyac140","type":"journal-article","created":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T20:05:12Z","timestamp":1662753912000},"source":"Crossref","is-referenced-by-count":19,"title":["Marker-assisted mapping enables forward genetic analysis in\n                    <i>Aedes aegypti<\/i>\n                    , an arboviral vector with vast recombination deserts"],"prefix":"10.1093","volume":"222","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9196-1274","authenticated-orcid":false,"given":"Chujia","family":"Chen","sequence":"first","affiliation":[{"name":"Genetics Bioinformatics and Computational Biology Program, Virginia Tech , Blacksburg, VA 24061, USA"},{"name":"Fralin Life Sciences Institute, Virginia Tech , Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin","family":"Compton","sequence":"additional","affiliation":[{"name":"Fralin Life Sciences Institute, Virginia Tech , Blacksburg, VA 24061, USA"},{"name":"Department of Biochemistry, Virginia Tech , Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Nikolouli","sequence":"additional","affiliation":[{"name":"Insect Pest Control Laboratory, Joint FAO\/IAEA Centre of Nuclear Techniques in Food and Agriculture, Department of Nuclear Sciences and Applications, IAEA Laboratories , 2444 Seibersdorf, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aihua","family":"Wang","sequence":"additional","affiliation":[{"name":"Fralin Life Sciences Institute, Virginia Tech , Blacksburg, VA 24061, USA"},{"name":"Department of Biochemistry, Virginia Tech , Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azadeh","family":"Aryan","sequence":"additional","affiliation":[{"name":"Fralin Life Sciences Institute, Virginia Tech , Blacksburg, VA 24061, USA"},{"name":"Department of Biochemistry, Virginia Tech , Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atashi","family":"Sharma","sequence":"additional","affiliation":[{"name":"Fralin Life Sciences Institute, Virginia Tech , Blacksburg, VA 24061, USA"},{"name":"Department of Biochemistry, Virginia Tech , Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumin","family":"Qi","sequence":"additional","affiliation":[{"name":"Fralin Life Sciences Institute, Virginia Tech , Blacksburg, VA 24061, USA"},{"name":"Department of Biochemistry, Virginia Tech , Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camden","family":"Dellinger","sequence":"additional","affiliation":[{"name":"Fralin Life Sciences Institute, Virginia Tech , Blacksburg, VA 24061, USA"},{"name":"Department of Biochemistry, Virginia Tech , Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Hempel","sequence":"additional","affiliation":[{"name":"Fralin Life Sciences Institute, Virginia Tech , Blacksburg, VA 24061, USA"},{"name":"Department of Biochemistry, Virginia Tech , Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Potters","sequence":"additional","affiliation":[{"name":"Fralin Life Sciences Institute, Virginia Tech , Blacksburg, VA 24061, USA"},{"name":"Department of Biochemistry, Virginia Tech , Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3682-6077","authenticated-orcid":false,"given":"Antonios","family":"Augustinos","sequence":"additional","affiliation":[{"name":"Insect Pest Control Laboratory, Joint FAO\/IAEA Centre of Nuclear Techniques in Food and Agriculture, Department of Nuclear Sciences and Applications, IAEA Laboratories , 2444 Seibersdorf, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W","family":"Severson","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Notre Dame , Notre Dame, IN 46556, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3999-4095","authenticated-orcid":false,"given":"Kostas","family":"Bourtzis","sequence":"additional","affiliation":[{"name":"Insect Pest Control Laboratory, Joint FAO\/IAEA Centre of Nuclear Techniques in Food and Agriculture, Department of Nuclear 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